bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term Health Outcomes of New Persistent Opioid Use After Surgery Among Medicare Beneficiaries
Authors: Santosa Katherine B. , Priest Caitlin R. , Oliver Jeremie D. , Kenney Brooke , Bicket Mark C. , Brummett Chad M. , Waljee Jennifer F.
Published: November 2022

Objective:

We examined long-term health outcomes associated with new persistent opioid use after surgery and hypothesized that patients with new persistent opioid use would have poorer overall health outcomes compared with those who did not develop new persistent opioid use after surgery.

Background:

New persistent opioid use is a common surgical complication. Long-term opioid use increases risk of mortality, fractures, and falls; however, less is known about health care utilization among older adults with new persistent opioid use after surgical care.

Methods:

We analyzed claims from a 20% national sample of Medicare beneficiaries ≥65 years undergoing surgery between January 1, 2009, and June 30, 2019. We estimated associations between new persistent use and subsequent health events between 6 and 12 months after surgery, including mortality, serious fall/fall-related injury, and respiratory or opioid/pain-related readmission/emergency department (ED) visits using a Cox proportional hazards model to estimate mortality and multivariable logistic regression for the remaining outcomes, adjusting for demographic/clinical characteristics. Our primary outcome was mortality within 6 to 12 months after surgery. Secondary outcomes included falls and readmissions or ED visits (respiratory, pain related/opioid related) within 6 to 12 months after surgery.

Results:

Of 229,898 patients, 6874 (3.0%) developed new persistent opioid use. Compared with patients who did not develop new persistent opioid use, patients with new persistent opioid use had a higher risk of mortality (hazard ratio 3.44, CI, 2.99–3.96), falls [adjusted odds ratio (aOR): 1.21, 95% CI, 1.05–1.39], and respiratory-related (aOR: 1.67, 95% CI, 1.49–1.86) or pain-related/opioid-related (aOR: 1.68, 95% CI, 1.55–1.82) readmissions/ED visits.

Conclusions:

New persistent opioid use after surgery is associated with increased mortality and poorer health outcomes after surgery. Although the mechanisms that underlie this risk are not clear, persistent opioid use may also be a marker for greater morbidity requiring more care in the late postoperative period. Increased awareness of individuals at risk for new persistent use after surgery and close follow-up in the late postoperative period is critical to mitigate the harms associated with new persistent use.
Suprapapillary Needle Knife Fistulotomy Versus Conventional Precut Sphincterotomy in Difficult Biliary Cannulation: A Retrospective Comparative Study
Authors: Başpinar Batuhan , Ödemiş Bülent , Erdoğan Çağdaş , Yüksel Mahmut
Published: November 2022

Background:

Endoscopic retrograde cholangiopancreatography (ERCP) is an important therapeutic tool for many biliary diseases. Selective biliary cannulation is the first step of the treatment process. Needle knife fistulotomy (NKF) and conventional precut sphincterotomy (CPS) are widely used in difficult biliary cannulation. However, there are different results in their effectiveness and safety. This study aimed to compare both methods regarding cannulation success and adverse event profile.

Materials and Methods:

All eligible consecutive patients with naive papillae who underwent biliary ERCP by a single experienced endoscopist over a 3-year period were included retrospectively. The standard cannulation method with a guidewire-loaded sphincterotome was initially used for biliary cannulation in all patients. Cannulation was accepted as difficult in the case of failure of standard cannulation within 5 minutes or despite 5 attempts or insertion of the guidewire to the pancreatic duct 5 times. Three modalities in patients with difficult biliary cannulation were employed according to the structure and configuration of the papillae in addition to unintentional pancreatic cannulation: (1) NKF, (2) CPS, (3) Double guidewire technique or guidewire orientation/precut following pancreatic stenting. Latter was excluded to enable direct comparison between NKF and CPS groups.

Results:

A total of 644 patients were recruited. Analyses were performed with 541 patients after the exclusion of 103 patients. Mean (SD) age was 60.4 (18.2) years, and 257 (47.5%) patients were male. While standard cannulation was successful in 366 (67.6%), difficult biliary cannulation was observed in 175 (32.4%) patients. NKF was performed in 101 (57.7%) patients, and cannulation success was 100% in the first ERCP session. In contrast, CPS was performed in 74 (42.3%) patients with a lower cannulation success rate (79.7%) than NKF (P<0.001). Post-ERCP pancreatitis rate was higher in CPS (9.5%) than NKF group (3.0%, P=0.063). Bleeding and cholangitis were similar in both groups.

Conclusions:

In patients with difficult biliary cannulation with appropriate papillary structure and configuration, NKF should be used as the first choice in experienced hands because of high biliary cannulation success and low Post-ERCP pancreatitis risk.
Assessing trauma readiness costs in level III and level IV trauma centers
Authors: Atkins Elizabeth V. , Vaughn Kelli A. , Medeiros Regina S. , Patterson Gregory K. , Register Alicia R. , Ashley Dennis W.
Published: November 2022

BACKGROUND

Readiness costs are expenses incurred by trauma centers to maintain essential infrastructure. Although the components for readiness are described in the American College of Surgeons' Resources for Optimal Care of the Injured Patient, the cost associated with each component is not well defined. Previous studies describe readiness costs for levels I and II trauma centers based on these criteria. The purpose of this study was to quantify the cost of levels III and IV trauma center readiness.

METHODS

The state trauma commission, along with trauma medical directors, program managers, and trauma center financial staff, standardized definitions for each component of trauma center readiness costs and developed a survey tool for reporting. Readiness costs were grouped into four categories: Administrative/Program Support Staff, Clinical Medical Staff, and Education/Outreach. A financial auditor analyzed all data to verify consistent cost reporting. Trauma center outliers were evaluated to validate variances. All levels III and IV trauma centers (n = 14) completed the survey on 2019 data.

RESULTS

Average annual readiness cost is $1,715,025 for a level III trauma center and $81,620 for level IV centers. Among the costliest components were clinical medical staff for level IIIs and administrative costs for level IVs, representing 54% and 97% of costs, respectively. Although education/outreach is mandated, levels III and IV trauma centers only spend approximately $8,000 annually on this category (0.8–3%).

CONCLUSION

This study defines the cost associated with each readiness component outlined in the Resources for Optimal Care of the Injured Patient manual. The average readiness cost for a level III trauma center is $1,715,025 and $81,620 for a level IV, underscoring the need for additional trauma center funding to meet the requirements set forth by the American College of Surgeons.

LEVEL OF EVIDENCE

Economic and Value-Based Evaluations; Level III.
Predictors of Length of Stay and Mortality During Simultaneous Liver-Kidney Transplant Index Admission: Results From the US-Multicenter SLKT Consortium
Authors: Barman Pranab M. , Patel Yuval A. , Xie Jiaheng , Zhang Min , Jo Jennifer , Sinha Jasmine , Answine Adeline , Schluger Aaron , Walter Kara , Biggins Scott W. , Cullaro Giuseppe , Wong Randi , Lai Jennifer C. , VanWagner Lisa B. , Magee John , Verna Elizabeth C. , Sharma Pratima
Published: November 2022

Background.

Length of stay (LOS) during index solid organ transplant impacts morbidity and healthcare costs. To date, there are no studies evaluating characteristics and outcomes of simultaneous liver-kidney transplant (SLKT) index hospitalization. We examined factors associated with LOS and mortality during index SLKT admission.

Methods.

Adult SLKT recipients between 2002 and 2017 at 6 transplant centers across 6 UNOS regions were retrospectively enrolled in the US-Multicenter SLKT Consortium. Multivariable regression analyses assessed predictors of SLKT LOS and death during index admission.

Results.

Median age of cohort (N = 570) was 58 y (interquartile range: 51–64); 63% male, 75% White, 32.3% hepatitis C, 23.3% alcohol-related, 20.1% nonalcoholic steatohepatitis with median MELD-Na at SLKT 28 (23–34). Seventy-one percent were hospitalized at the time of SLKT with median LOS pretransplant of 10 d. Majority of patients were discharged alive (N = 549; 96%)‚ and 36% were discharged to subacute rehab facility. LOS for index SLKT was 19 d (Q1: 10, Q3: 34 d). Female sex (P = 0.003), Black race (P = 0.02), advanced age (P = 0.007), ICU admission at time of SLKT (P = 0.03), high MELD-Na (P = 0.003), on cyclosporine during index hospitalization (P = 0.03), pre-SLKT dialysis (P < 0.001), and kidney delayed graft function (P < 0.001) were the recipient factors associated with prolonged LOS during index SLKT hospitalization. Prolonged LOS also contributed to overall mortality (HR = 1.007; P = 0.03).

Conclusions.

Despite excellent survival, index SLKT admission was associated with high-resource utilization with more than half the patients with LOS >2 wk and affected overall patient survival. Further investigation is needed to optimize healthcare resources for these patients in a financially strained healthcare landscape.
Temporal Trends in Portopulmonary Hypertension Model for End-stage Liver Disease Exceptions and Outcomes
Authors: del Valle Kathryn T. , Krowka Michael J. , Heimbach Julie K. , Taner Timucin , DuBrock Hilary M.
Published: November 2022

Background.

Model for end-stage liver disease (MELD) exception criteria for portopulmonary hypertension (POPH) were created to prioritize patients for liver transplant before POPH progression. Little is known about trends in POPH exception frequency, disease severity, pulmonary hypertension treatment patterns, or outcomes since the POPH MELD exception began.

Methods.

Using data from the Organ Procurement and Transplantation Network database, we describe the frequency of POPH MELD exceptions between 2006 and 2019, compare baseline patient characteristics, and characterize trends in liver disease and POPH severity‚ as well as POPH treatment and outcomes‚ over time. To facilitate comparison, we divided this 14-y period into 3 “eras” (2006–2010, 2011–2015, and 2016–2019).

Results.

Between 2006 and 2019, 504 unique POPH MELD exceptions were granted. Both liver disease severity and patient age have increased over time (P = 0.04 and P = 0.006, respectively). Posttreatment hemodynamic values (mean pulmonary arterial pressure and pulmonary vascular resistance) have significantly improved (P < 0.001 and P = 0.008, respectively). Treatment with endothelin receptor antagonists has become more prevalent, whereas use of parenteral therapy and monotherapy regimens has decreased (P < 0.001). Neither waitlist nor liver transplant mortality outcomes have significantly changed over the eras analyzed.

Conclusions.

In conclusion, 504 patients have received POPH MELD exceptions between 2006 and 2019. Since 2010, nearly all patients granted POPH MELD exceptions have met hemodynamic criteria for POPH. Over time, there has been a trend toward older age and higher MELD scores with significant changes in pulmonary arterial hypertension treatment patterns and an improvement in posttreatment hemodynamics without major change in outcomes.
Pressure injury prevention in adult critically ill patients: best practice implementation project
Authors: Ramalho Aline de Oliveira , Santiago Leidiane Moreira , Meira Luciana , Marin Alessandra , de Oliveira Larissa Bertacchini , Püschel Vilanice Alves de Araújo
Published: November 2022

Objective:

This study assessed compliance with the best practices for pressure injury prevention among ICU patients at a tertiary hospital in São Paulo, Brazil.

Introduction:

Intensive care patients are at high risk of developing a pressure injury; preventing this requires a best practice protocol.

Method:

This best practice implementation project was conducted in a Brazilian tertiary hospital in three phases following the JBI Model of Evidence-based Healthcare. Ten criteria derived from the best available evidence were audited and monitored before and after best practice implementation.

Results:

The baseline and follow-up audits evaluated 28 patients at each step. A total of 448 h of care were analyzed using a monitoring camera and medical records. Compliance with all 10 audited criteria increased, with a 50% reduction in the prevalence of pressure injuries in intensive care. Of the 223 employees, 71% claimed to have some knowledge of pressure injury prevention, and 66% reported adequate adherence to prevention protocols.

Conclusion:

The audit and feedback strategy improved compliance with the criteria. Future audits are needed to promote the sustainability of evidence-based practice.
Fifteen essential science advances needed for effective restoration of the world's forest landscapes
Authors: Marshall Andrew R. , Waite Catherine E. , Pfeifer Marion , Banin Lindsay F. , Rakotonarivo Sarobidy , Chomba Susan , Herbohn John , Gilmour Donald A. , Brown Mark , Chazdon Robin L.
Published: November 2022

There has never been a more pressing and opportune time for science and practice to collaborate towards restoration of the world's forests. Multiple uncertainties remain for achieving successful, long-term forest landscape restoration (FLR). In this article, we use expert knowledge and literature review to identify knowledge gaps that need closing to advance restoration practice, as an introduction to a landmark theme issue on FLR and the UN Decade on Ecosystem Restoration. Aligned with an Adaptive Management Cycle for FLR, we identify 15 essential science advances required to facilitate FLR success for nature and people. They highlight that the greatest science challenges lie in the conceptualization, planning and assessment stages of restoration, which require an evidence base for why, where and how to restore, at realistic scales. FLR and underlying sciences are complex, requiring spatially explicit approaches across disciplines and sectors, considering multiple objectives, drivers and trade-offs critical for decision-making and financing. The developing tropics are a priority region, where scientists must work with stakeholders across the Adaptive Management Cycle. Clearly communicated scientific evidence for action at the outset of restoration planning will enable donors, decision makers and implementers to develop informed objectives, realistic targets and processes for accountability. This article paves the way for 19 further articles in this theme issue, with author contributions from across the world.

This article is part of the theme issue ‘Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration’.
A practice-led assessment of landscape restoration potential in a biodiversity hotspot
Authors: Wills Abigail R. , Shirima Deo D. , Villemaire-Côté Olivier , Platts Philip J. , Knight Sarah J. , Loveridge Robin , Seki Hamidu , Waite Catherine E. , Munishi Pantaleo K. T. , Lyatuu Herman , Bernal Blanca , Pfeifer Marion , Marshall Andrew R.
Published: November 2022

Effective restoration planning tools are needed to mitigate global carbon and biodiversity crises. Published spatial assessments of restoration potential are often at large scales or coarse resolutions inappropriate for local action. Using a Tanzanian case study, we introduce a systematic approach to inform landscape restoration planning, estimating spatial variation in cost-effectiveness, based on restoration method, logistics, biomass modelling and uncertainty mapping. We found potential for biomass recovery across 77.7% of a 53 000 km
2
region, but with some natural spatial discontinuity in moist forest biomass, that was previously assigned to human causes. Most areas with biomass deficit (80.5%) were restorable through passive or assisted natural regeneration. However, cumulative biomass gains from planting outweighed initially high implementation costs meaning that, where applicable, this method yielded greater long-term returns on investment. Accounting for ecological, funding and other uncertainty, the top 25% consistently cost-effective sites were within protected areas and/or moderately degraded moist forest and savanna. Agro-ecological mosaics had high biomass deficit but little cost-effective restoration potential. Socio-economic research will be needed to inform action towards environmental and human development goals in these areas. Our results highlight value in long-term landscape restoration investments and separate treatment of savannas and forests. Furthermore, they contradict previously asserted low restoration potential in East Africa, emphasizing the importance of our regional approach for identifying restoration opportunities across the tropics.

This article is part of the theme issue ‘Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration’.
Identifying hotspots for ecosystem restoration across heterogeneous tropical savannah-dominated regions
Authors: Lewis Kennedy , Barros Fernanda de V. , Moonlight Peter W. , Hill Timothy C. , Oliveira Rafael S. , Schmidt Isabel B. , Sampaio Alexandre B. , Pennington R. Toby , Rowland Lucy
Published: November 2022

There is high potential for ecosystem restoration across tropical savannah-dominated regions, but the benefits that could be gained from this restoration are rarely assessed. This study focuses on the Brazilian Cerrado, a highly species-rich savannah-dominated region, as an exemplar to review potential restoration benefits using three metrics: net biomass gains, plant species richness and ability to connect restored and native vegetation. Localized estimates of the most appropriate restoration vegetation type (grassland, savannah, woodland/forest) for pasturelands are produced. Carbon sequestration potential is significant for savannah and woodland/forest restoration in the seasonally dry tropics (net biomass gains of 58.2 ± 37.7 and 130.0 ± 69.4 Mg ha−1). Modelled restoration species richness gains were highest in the central and south-east of the Cerrado for savannahs and grasslands, and in the west and north-west for woodlands/forests. The potential to initiate restoration projects across the whole of the Cerrado is high and four hotspot areas are identified. We demonstrate that landscape restoration across all vegetation types within heterogeneous tropical savannah-dominated regions can maximize biodiversity and carbon gains. However, conservation of existing vegetation is essential to minimizing the cost and improving the chances of restoration success.

This article is part of the theme issue ‘Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration’.
Forest restoration in a time of fire: perspectives from tall, wet eucalypt forests subject to stand-replacing wildfires
Authors: Lindenmayer David B. , Bowd Elle J. , Gibbons Philip
Published: November 2022

Wildfires have the potential to add considerably to the already significant challenge of achieving effective forest restoration in the UN Decade on Ecosystem Restoration. While fire can sometimes promote forest restoration (e.g. by creating otherwise rare, early successional habitats), it can thwart it in others (e.g. by depleting key patch types and stand structures). Here we outline key considerations in facilitating restoration of some tall wet temperate forest ecosystems and some boreal forest ecosystems where the typical fire regime is rare high-severity stand-replacing fire. Some of these ecosystems are experiencing altered fire regimes such as increased fire extent, severity and/or frequency. Achieving good restoration outcomes in such ecosystems demands understanding fire regimes and their impacts on vegetation and other elements of biodiversity and then selecting ecosystem-appropriate management interventions. Potential actions range from doing nothing (as the ecosystem already maintains full post-fire regenerative capacity) to interventions prior to a conflagration like prescribed burning to limit the risks of high-severity fire, excluding activities that impair post-fire recovery (e.g. post-fire logging), and artificial seeding where natural regeneration fails. The most ecologically effective actions will be ecosystem-specific and context-specific and informed by knowledge of the ecosystem in question (such as plant life-history attributes) and inter-relationships with attributes like vegetation condition at the time it is burnt (e.g. young versus old forest).

This article is part of the theme issue ‘Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration’.
Genomic insights into antibiotic-resistance and virulence genes of Enterococcus faecium strains from the gut of Apis mellifera
Authors: Zaghloul Heba A. H. , El Halfawy Nancy M.
Published: November 2022

Enterococcus faecium

is a lactic acid bacterium that confers beneficial health effects in humans. However, lately, a number of

E. faecium

strains have been linked to the spread of nosocomial infections in the hospital environment. Therefore, any potential commercial usage of

E. faecium

isolates should be preceded by an assessment of infection risk. In the current study, the genomes of two novel

E. faecium

strains Am1 (larval isolate) and Bee9 (adult bee isolate) isolated from the gut of Apis mellifera L. (honeybee) were sequenced to allow evaluation of their safety. In particular, their genomes were screened for antibiotic-resistance and virulence genes. In addition, their potential to spread resistance in the environment was evaluated. The analysis revealed that Am1 and Bee9 possess 2832 and 2844 protein-encoding genes, respectively. In each case, the genome size was 2.7 Mb with a G+C content of 37.9 mol%. Comparative analysis with probiotic, non-pathogenic and pathogenic enterococci revealed that there are variations between the two bee

E. faecium

isolates and pathogenic genomes. They were, however, closely linked to the probiotic comparison strains. Phenotypically, the Am1 and Bee9 strains were susceptible to most antibiotics tested, but showed intermediate sensitivity towards erythromycin, linezolid and trimethoprim/sulfamethoxazole. Notably, no genes associated with antibiotic resistance in clinical isolates (e.g. vancomycin resistance: vanA, vanB, vanS, vanX and vanY) were present. In addition, the insertion sequences (IS16, ISEfa11 and ISEfa5), acting as molecular pathogenicity markers in clinically relevant

E. faecium

strains, were also absent. Moreover, the analysis revealed the absence of three key pathogenicity-associated genes (acm, sgrA, ecbA) in the Am1 and Bee9 strains that are found in the prominent clinical isolates DO, V1836, Aus0004 and Aus0085. Overall, the findings of this investigation suggest that the

E. faecium

isolates from the bee gut have not suffered any recent clinically relevant antibiotic exposure. It also suggests that

E. faecium

Am1 and Bee9 are safe potential probiotic strains, because they lack the phenotypic and genetic features associated with strains eliciting nosocomial infections.
The phenotypic spectrum of terminal and subterminal 6p deletions based on a social media-derived cohort and literature review
Authors: Rraku Eleana , Kerstjens-Frederikse Wilhelmina S. , Swertz Morris A. , Dijkhuizen Trijnie , van Ravenswaaij-Arts Conny M. A. , Engwerda Aafke
Published: November 2022

Background

Terminal 6p deletions are rare, and information on their clinical consequences is scarce, which impedes optimal management and follow-up by clinicians. The parent-driven Chromosome 6 Project collaborates with families of affected children worldwide to better understand the clinical effects of chromosome 6 aberrations and to support clinical guidance. A microarray report is required for participation, and detailed phenotype information is collected directly from parents through a multilingual web-based questionnaire. Information collected from parents is then combined with case data from literature reports. Here, we present our findings on 13 newly identified patients and 46 literature cases with genotypically well-characterised terminal and subterminal 6p deletions. We provide phenotype descriptions for both the whole group and for subgroups based on deletion size.

Results

The total group shared a common phenotype characterised by ocular anterior segment dysgenesis, vision problems, brain malformations, congenital defects of the cardiac septa and valves, mild to moderate hearing impairment, eye movement abnormalities, hypotonia, mild developmental delay and dysmorphic features. These characteristics were observed in all subgroups, confirming a dominant role forFOXC1, one of the most distally deleted genes. Additional characteristics were seen in individuals with terminal deletions exceeding 4.02 Mb, namely complex heart defects, corpus callosum abnormalities, kidney abnormalities and orofacial clefting. Some of these additional features may be related to the loss of other genes in the terminal 6p region, such asRREB1for the cardiac phenotypes andTUBB2AandTUBB2Bfor the cerebral phenotypes. In the newly identified patients, we observed previously unreported features including gastrointestinal problems, neurological abnormalities, balance problems and sleep disturbances.

Conclusions

We present an overview of the phenotypic characteristics observed in terminal and subterminal 6p deletions. This reveals a common phenotype that can be highly attributable to haploinsufficiency ofFOXC1, with a possible additional effect of other genes in the 6p25 region. We also delineate the developmental abilities of affected individuals and report on previously unrecognised features, showing the added benefit of collecting information directly from parents. Based on our overview, we provide recommendations for clinical surveillance to support clinicians, patients and families.
The phenotypic spectrum of terminal 6q deletions based on a large cohort derived from social media and literature: a prominent role forDLL1
Authors: Engwerda Aafke , Kerstjens-Frederikse Wilhelmina S. , Corsten-Janssen Nicole , Dijkhuizen Trijnie , van Ravenswaaij-Arts Conny M. A.
Published: November 2022

Background

Terminal 6q deletions are rare, and the number of well-defined published cases is limited. Since parents of children with these aberrations often search the internet and unite via international social media platforms, these dedicated platforms may hold valuable knowledge about additional cases. The Chromosome 6 Project is a collaboration between researchers and clinicians at the University Medical Center Groningen and members of a Chromosome 6 support group on Facebook. The aim of the project is to improve the surveillance of patients with chromosome 6 aberrations and the support for their families by increasing the available information about these rare aberrations. This parent-driven research project makes use of information collected directly from parents via a multilingual online questionnaire. Here, we report our findings on 93 individuals with terminal 6q deletions and 11 individuals with interstitial 6q26q27 deletions, a cohort that includes 38 newly identified individuals.

Results

Using this cohort, we can identify a common terminal 6q deletion phenotype that includes microcephaly, dysplastic outer ears, hypertelorism, vision problems, abnormal eye movements, dental abnormalities, feeding problems, recurrent infections, respiratory problems, spinal cord abnormalities, abnormal vertebrae, scoliosis, joint hypermobility, brain abnormalities (ventriculomegaly/hydrocephaly, corpus callosum abnormality and cortical dysplasia), seizures, hypotonia, ataxia, torticollis, balance problems, developmental delay, sleeping problems and hyperactivity. Other frequently reported clinical characteristics are congenital heart defects, kidney problems, abnormalities of the female genitalia, spina bifida, anal abnormalities, positional foot deformities, hypertonia and self-harming behaviour. The phenotypes were comparable up to a deletion size of 7.1 Mb, and most features could be attributed to the terminally located geneDLL1. Larger deletions that includeQKI(>7.1 Mb) lead to a more severe phenotype that includes additional clinical characteristics.

Conclusions

Terminal 6q deletions cause a common but highly variable phenotype. Most clinical characteristics can be linked to the smallest terminal 6q deletions that include the geneDLL1(>500 kb). Based on our findings, we provide recommendations for clinical follow-up and surveillance of individuals with terminal 6q deletions.
Protection against infection with the Omicron BA.5 subvariant among people with previous SARS-CoV-2 infection - surveillance results from southern Sweden, June to August 2022
Authors: Kahn Fredrik , Bonander Carl , Moghaddassi Mahnaz , Bennet Louise , Malmqvist Ulf , Inghammar Malin , Björk Jonas
Published: November 2022

We evaluated the protection afforded by SARS-CoV-2 natural infection against reinfection among vaccinated during a calendar period from June to August 2022 when Omicron BA.5 was the dominating subvariant in Scania county, Sweden. We formed a study cohort (n = 71 592) mainly consisting of health care workers by restricting to people 18-64 years old who received their first vaccine dose relatively early (24 April 2021 or sooner). We used continuous density case-control 1:10 sampling matched for sex and age within the study cohort, and thereby obtained 1 114 cases during Omicron BA.5 dominance and 11 140 controls who were analysed with conditional logistic regression. Limited protection against reinfection was suggested from prior infection of virus variants before Omicron (11%, 95% confidence interval [CI] −10 to 28%]. By contrast, prior Omicron infection offered clear protection (65%, 95% CI 56-73%). For the Omicron BA.2 subvariant, stronger protection was suggested during early (85%, 95% CI 75-91%) than later BA.5 dominance (66%, 95% CI 48-78%). Lower protection was observed from the previous BA.1 subvariant (30%; 95% CI −4 to 53%). These findings suggest that natural infection from the Omicron subvariants contributes to short-term population protection against reinfection with the subvariant BA.5 among vaccinated, but wanes considerably 5-6 months after infection.
Successful Detection of Delta and Omicron Variants of SARS-CoV-2 by Veterinary Diagnostic Laboratory Participants in an Interlaboratory Comparison Exercise
Authors: Deng Kaiping , Nemser Sarah M. , Frost Kirstin , Goodman Laura B. , Ip Hon S. , Killian Mary Lea , Ulaszek Jodie , Kiener Shannon , Kmet Matthew , Uhlig Steffen , Hettwer Karina , Colson Bertrand , Nichani Kapil , Schlierf Anja , Tkachenko Andriy , Miller Megan R. , Reddy Ravinder , Tyson Gregory H.
Published: November 2022

Background

Since the beginning of the COVID-19 pandemic veterinary diagnostic laboratories have tested diagnostic samples for SARS-CoV-2 not only in animals, but in over five million human samples. An evaluation of the performance of those laboratories is needed using blinded test samples to ensure that laboratories report reliable data to the public. This interlaboratory comparison exercise (ILC3) builds on two prior exercises to assess whether veterinary diagnostic laboratories can detect Delta and Omicron variants spiked in canine nasal matrix or viral transport medium.

Methods

Inactivated Delta variant at levels of 25 to 1,000 copies per 50 μL of nasal matrix were prepared for participants by the ILC organizer, an independent laboratory, for blinded analysis. Omicron variant at 1,000 copies per 50 μL of transport medium was also included. Feline infectious peritonitis virus (FIPV) RNA was used as a confounder for specificity assessment. A total of 14 test samples were prepared for each participant. Participants used their routine diagnostic procedures for RNA extraction and real-time RT-PCR. Results were analyzed according to International Organization for Standardization (ISO) 16140 - 2:2016.

Results

The overall results showed 93% detection for Delta and 97% for Omicron at 1,000 copies per 50 μL (22-200 copies per reaction). The overall specificity was 97% for blank samples and 100% for blank samples with FIPV. No differences in Ct values were significant for samples with the same virus levels between N1 and N2 markers, nor between the two variants.

Conclusions

The results indicated that all ILC3 participants were able to detect both Delta and Omicron variants. The canine nasal matrix did not significantly affect SARS-CoV-2 detection.

Impact Statement

Ensuring accurate detection methods for SARS-CoV-2 is critical as veterinary diagnostic labs are testing both human and animal samples. This exercise used blinded test samples and provided high confidence in the sensitivity of methods in twenty-nine laboratories for detection of SARS-CoV-2 variants while addressing the impact of sample matrix. Importantly, the results indicated that variants and matrix do not impact detection results. Additionally, this article examined decision-making criteria for Ct cut-off values from different laboratories and encouraged them to review and potentially reassess their criteria to improve future performance. This knowledge will lead to higher confidence in laboratory detection of current and new SARS-CoV-2 variants and aid in establishing reasonable cut-off parameters for these diagnostics tests.
Near-Physiological in vitro Assembly of 50S Ribosomes Involves Parallel Pathways
Authors: Dong Xiyu , Doerfel Lili K. , Sheng Kai , Rabuck-Gibbons Jessica N. , Popova Anna M. , Lyumkis Dmitry , Williamson James R.
Published: November 2022

Understanding the assembly principles of biological macromolecular complexes remains a significant challenge, due to the complexity of the systems and the difficulties in developing experimental approaches. As a ribonucleoprotein complex, the ribosome serves as an ideal model system for the profiling of macromolecular complex assembly. In this work, we report an ensemble of large ribosomal subunit intermediate structures that accumulate during synthesis in a near-physiological and co-transcriptionalin vitroreconstitution system. Thirteen pre-50S intermediate maps covering the whole assembly process were resolved using cryo-EM single particle analysis and heterogeneous subclassification. Segmentation of the set of density maps reveals that the 50S ribosome intermediates assemble based on fourteen cooperative assembly blocks, including the smallest assembly core reported up to now, which is composed of a 600-nucleotide-long folded rRNA and three ribosomal proteins. The cooperative blocks assemble onto the assembly core following a defined set of dependencies, revealing the parallel assembly pathways at both early and late assembly stages of the 50S subunit.
Validation of predicted conformal intervals for prediction of human clinical pharmacokinetics
Authors: Fagerholm Urban , Alvarsson Jonathan , Hellberg Sven , Spjuth Ola
Published: November 2022

Introduction

Conformal prediction (CP) methodology sits on top of machine learning methods and produces prediction confidence intervals that depend on how “strange” (non-conforming) test compounds are compared to training set compounds. CP has previously been successfully applied for prediction of steady-state volume of distribution (Vss) in humans, with 69 % of observations within the prediction interval at a 70 % confidence level. We have developed CP models for a variety of human pharmacokinetic (PK) parameters and validated their predictive accuracy (predictedvsobserved estimates), but not validated prediction confidence intervals for them. The main objective of this study was to predict 70 % confidence intervals for Vss, unbound fraction in plasma (fu), intrinsic metabolic clearance (CLint), fraction absorbed passively (fa,passive) and maximum fraction dissolved (fdiss) for a variety of compounds in man and investigate the consistency between prediction intervals and observed/measured values.

Methodology

CP models featured in the ANDROMEDA software by Prosilico were used for prediction of 70 % confidence intervals of Vss, fu, CLint, fa,passiveand fdissfor compounds from different chemical classes and with broad physicochemical variety and for small drugs marketed in 2021.

Results

70 % prediction confidence intervals for 217, 117, 117, 89 and 89 compounds were produced for Vss, fu, CLint, fa,passiveand fdiss, respectively. 78 % (expected 70 %) of observed data were within 70 % confidence intervals for the parameters. 70 % of predictions of Vss, fu, CLintfa,passiveand fdissare expected to have errors of maximally 2-, 4- and 6-fold and 7 and 12 %, respectively, which is in line with prediction errors. These findings validate the CP methodology.

Conclusion

In conclusion, the results further validate CP models and confidence intervals of ANDROMEDA for prediction of human PK.
Degree-day-based model to predict egg hatching ofPhilaenus spumarius(Hemiptera: Aphrophoridae), the main vector ofXylella fastidiosain Europe
Authors: Lago Clara , Gimenez-Romero Alex , Morente Marina , Matías Manuel A. , Moreno Aránzazu , Fereres Alberto
Published: November 2022

Philaenus spumariusL., the main vector ofXylella fastidiosa(Wells) in Europe, is a univoltine species that overwinters in the egg stage, and its nymphs emerge in late winter or spring. Predicting the time of egg hatching is essential for determining the precise times for deploying control strategies against insect pests. Here, we monitoredP. spumariuseggs from oviposition to egg hatching together with the daily temperatures and relative humidities at four field locations that were located at different altitudes in central Spain. The collected data were used to build a growing degree day (GDD) model to forecast egg hatching in the Iberian Peninsula. Furthermore, the model was validated with field observations that were conducted in Spain. The model was then used as a decision-support tool to calculate the optimum timing for applying control actions againstP. spumarius. Our results suggest that controlling nymphs at two different dates would target the highest percentages of nymphal populations present in the field. Our model represents a first step for predicting the emergence of nymphs and adopting timely control actions againstP. spumarius. These actions could limit disease spread in areas whereX. fastidiosais present.
Encoding of 2D self-centered plans and world-centered positions in the rat frontal orienting field
Authors: Li Liujunli , Flesch Timo , Ma Ce , Li Jingjie , Chen Yizhou , Chen Hung-Tu , Erlich Jeffrey C.
Published: November 2022

The neural mechanisms of motor planning have been extensively studied in rodents. Preparatory activity in the frontal cortex predicts upcoming choice, but limitations of typical tasks have made it challenging to determine whether the spatial information is in a self-centered direction reference frame or a world-centered position reference frame. Here, we trained rats to make delayed visually-guided orienting movements to six different directions, with four different target positions for each direction, which allowed us to disentangle direction versus position tuning in neural activity. We recorded single unit activity from the rat frontal orienting field (FOF) in the secondary motor cortex, a region involved in planning orienting movements. Population analyses revealed that the FOF encodes two separate 2D maps of space. First, a 2D map of the planned and ongoing movement in a self-centered direction reference frame. Second, a 2D map of the animal’s current position on the port wall in a world-centered reference frame. Thus, preparatory activity in the FOF represents self-centered upcoming movement directions, but FOF neurons multiplex both self- and world-reference frame variables at the level of single neurons. Neural network model comparison supports the view that despite the presence of world-centered representations, the FOF receives the target information as self-centered input and generates self-centered planning signals.
Optopharmacological tools for precise spatiotemporal control of oxytocin signaling in the central nervous system and periphery
Authors: Ahmed Ismail A. , Liu Jing-Jing , Gieniec Krystyna A. , Bair-Marshall Chloe J. , Adewakun Ayomiposi B. , Hetzler Belinda E. , Arp Christopher J. , Khatri Latika , Vanwalleghem Gilles C. , Seidenberg Alec T. , Cowin Pamela , Trauner Dirk , Chao Moses V. , Davis Felicity M. , Tsien Richard W. , Froemke Robert C.
Published: November 2022

Oxytocin is a neuropeptide critical for maternal physiology and social behavior, and is thought to be dysregulated in several neuropsychiatric disorders. Despite the biological and neurocognitive importance of oxytocin signaling, methods are lacking to activate oxytocin receptors with high spatiotemporal precision in the brain and peripheral mammalian tissues. Here we developed and validated caged analogs of oxytocin which are functionally inert until cage release is triggered by ultraviolet light. We examined how focal versus global oxytocin application affected oxytocin-driven Ca2+wave propagation in mouse mammary tissue. We also validated the application of caged oxytocin in the hippocampus and auditory cortex with electrophysiological recordingsin vitro, and demonstrated that oxytocin uncaging can accelerate the onset of mouse maternal behaviorin vivo. Together, these results demonstrate that optopharmacological control of caged peptides is a robust tool with spatiotemporal precision for modulating neuropeptide signaling throughout the brain and body.
Anatomy Segmentation in Laparoscopic Surgery: Comparison of Machine Learning and Human Expertise – An Experimental Study
Authors: Kolbinger Fiona R. , Rinner Franziska M. , Jenke Alexander C. , Carstens Matthias , Krell Stefanie , Leger Stefan , Distler Marius , Weitz Jürgen , Speidel Stefanie , Bodenstedt Sebastian
Published: November 2022

Structured Abstract

Background

Lack of anatomy recognition represents a clinically relevant risk in abdominal surgery. Machine learning (ML) methods can help identify visible patterns and risk structures, however, their practical value remains largely unclear.

Materials and Methods

Based on a novel dataset of 13195 laparoscopic images with pixel-wise segmentations of eleven anatomical structures, we developed specialized segmentation models for each structure and combined models for all anatomical structures using two state-of-the-art model architectures (DeepLabv3 and SegFormer), and compared segmentation performance of algorithms to a cohort of 28 physicians, medical students, and medical laypersons using the example of pancreas segmentation.

Results

Mean Intersection-over-Union for semantic segmentation of intraabdominal structures ranged from 0.28 to 0.83 and from 0.23 to 0.77 for the DeepLabv3-based structure-specific and combined models, and from 0.31 to 0.85 and from 0.26 to 0.67 for the SegFormer-based structure-specific and combined models, respectively. Both the structure-specific and the combined DeepLabv3-based models are capable of near-real-time operation, while the SegFormer-based models are not. All four models outperformed at least 26 out of 28 human participants in pancreas segmentation.

Conclusions

These results demonstrate that ML methods have the potential to provide relevant assistance in anatomy recognition in minimally-invasive surgery in near-real-time. Future research should investigate the educational value and subsequent clinical impact of respective assistance systems.

Highlights

Machine learning models to reduce surgical risks that precisely identify 11 anatomical structures: abdominal wall, colon, intestinal vessels (inferior mesenteric artery and inferior mesenteric vein with their subsidiary vessels), liver, pancreas, small intestine, spleen, stomach, ureter and vesicular glands

Large training dataset of 13195 real-world laparoscopic images with high-quality anatomy annotations

Similar performance of individual segmentation models for each structure and combined segmentation models in identifying intraabdominal structures, and similar segmentation performance of DeepLabv3-based and SegFormer-based models

DeepLabv3-based models are capable of near-real-time operation while SegFormer-based models are not, but SegFormer-based models outperform DeepLabv3-based models in terms of accuracy and generalizability

All models outperformed at least 26 out of 28 human participants in pancreas segmentation, demonstrating their potential for real-time assistance in recognizing anatomical landmarks during minimally-invasive surgery.
Serial dependence in timing at the perceptual level being modulated by working memory
Authors: Chen Shuai , Wang Tianhe , Bao Yan
Published: November 2022

Recent experiences bias the perception of following stimuli, as has been verified in various kinds of experiments in visual perception. This phenomenon, known as serial dependence, may reflect mechanisms to maintain perceptual stability. In the current study, we examined several key properties of serial dependence in temporal perception. Firstly, we examined the source of serial dependence effect in temporal perception. We found that perception without motor reproduction is sufficient to induce the sequential effect; the motor reproduction caused a stronger effect and it is achieved by biasing the perception of the future target duration rather than directly influences the subsequent movement. Secondly, we ask how the working memory influences serial dependence in the in a temporal reproduction task. By varying the delay time between standard duration and the reproduction, we showed that the strength of serial dependence enhanced as the delay increased. Those features of serial dependence are consistent with what has been observed in the visual perceptual tasks, for example, orientation perception or location perception. The similarities between the visual and the timing tasks may suggest a similar neural coding mechanism of magnitude between the visual stimuli and the duration.