bluuebunny/crossref_metadata_2025 huggingface dataset:
Facial Fractures in Indigenous and Non-indigenous Populations of South Australia
Authors: Diab Jason , Flapper Walter J. , Moore Mark H.
Published: January 2023

Introduction:

Maxillofacial trauma in indigenous populations is complex with sociocultural factors, access to health care, and poorer general health issues that impact outcomes. Assaults and road traffic accidents are disproportionately experienced by indigenous persons compared with non-indigenous.

Methods:

A retrospective review was conducted from January 2012 to January 2017 at the Women and Children’s Hospital and Royal Adelaide Hospital, Adelaide. All maxillofacial fractures that attended or were referred to the unit were included in this study. The primary objective was to analyze epidemiological trends of facial fractures and clinical outcomes in the South Australian indigenous and non-indigenous populations.

Results:

Maxillofacial fractures in indigenous persons were less than in non-indigenous (31.2 versus 38.2 y, P < 0.001) with 3.8 odds of a facial fracture. Assault was 2.9 times more likely to result in a facial fracture, falls 40.9% less likely, and sports 29.4% less likely compared with non-indigenous (P < 0.001). Alcohol-related facial fractures had significantly higher rates [odds ratio (OR = 3.8)] compared with non-indigenous. Indigenous from most disadvantaged areas and very remote areas also had significantly higher odds of a facial fracture. Indigenous persons had higher operative rates (OR = 2.8), postoperative complications (OR = 3.1), and a 3.7-day mean difference for the length of stay (6.6 versus 2.9 d, P < 0.001).

Conclusions:

Indigenous people are more likely to experience facial fractures from assault resulting in mandibular fractures, whereas non-indigenous people are likely to have sport or fall-related midface fractures. Young indigenous women from outer regional and very remote areas have greater odds of facial fractures caused by assault and alcohol with higher operative rates, postoperative complications, and extended length of stay.
The High Incidence of Occult Carcinoma in Total Hepatectomy Specimens of Patients Treated for Unresectable Colorectal Liver Metastases With Liver Transplant
Authors: Chávez-Villa Mariana , Ruffolo Luis I. , Al-Judaibi Bandar M. , Fujiki Masato , Hashimoto Koji , Kallas Jeffrey , Kwon Choon Hyuck David , Nair Amit , Orloff Mark S. , Pineda-Solis Karen , Raj Roma , Sasaki Kazunari , Tomiyama Koji , Aucejo Federico , Hernandez-Alejandro Roberto
Published: January 2023

Objective:

To describe the rate of occult carcinoma deposits in total hepatectomy specimens from patients treated with liver transplant (LT) for colorectal liver metastases (CRLM).

Background:

Previous studies have shown that patients with CRLM treated with systemic therapy demonstrate a high rate of complete radiographic response or may have disappearing liver metastases. However, this does not necessarily translate into a complete pathologic response, and residual invasive cancer may be found in up to 80% of the disappearing tumors after resection.

Methods:

Retrospective review of 14 patients who underwent LT for CRLM, at 2 centers. Radiographic and pathologic correlation of the number of tumors and their viability before and after LT was performed.

Results:

The median (interquartile range) number of tumors at diagnosis was 11 (4–23). The median number of chemotherapy cycles was 24 (16–37). Hepatic artery infusion was used in 5 patients (35.7%); 6 (42.9%) underwent surgical resection, and 5 (35.7%) received locoregional therapy. The indication for LT was unresectability in 8 patients (57.1%) and liver failure secondary to oncologic treatment in the remaining 6 (42.9%). Before LT, 7 patients (50%) demonstrated fluorodeoxyglucose-avid tumors and 7 (50%) had a complete radiographic response. Histopathologically, 11 patients (78.6%) had a viable tumor. Nine (64.2%) of the 14 patients were found to have undiagnosed metastases on explant pathology, with at least 22 unaccounted viable tumors before LT. Furthermore, 4 (57.1%) of the 7 patients who demonstrated complete radiographic response harbored viable carcinoma on explant pathology.

Conclusions:

A complete radiographic response does not reliably predict a complete pathologic response. In patients with unresectable CRLM, total hepatectomy and LT represent a promising treatment options to prevent indolent disease progression from disappearing CRLM.
Adverse Events and Morbidity in a Multidisciplinary Pediatric Robotic Surgery Program. A prospective, Observational Study
Authors: Vinit Nicolas , Vatta Fabrizio , Broch Aline , Hidalgo Mary , Kohaut Jules , Querciagrossa Stefania , Couloigner Vincent , Khen-Dunlop Naziha , Botto Nathalie , Capito Carmen , Sarnacki Sabine , Blanc Thomas
Published: January 2023

Objective:

To report one-year morbidity of robotic-assisted laparoscopic surgery (RALS) in a dedicated, multidisciplinary, pediatric robotic surgery program. Summary Background Data. RALS in pediatric surgery is expanding, but data on morbidity in children is limited.

Methods:

All children who underwent RALS (Da Vinci Xi, Intuitive Surgical, USA) were prospectively included (October 2016 to May 2020; follow-up ≥1 year). Analyzed data: patient characteristics, surgical indication/procedure, intraoperative adverse events (ClassIntra classification), blood transfusion, hospital stay, postoperative complications (Clavien-Dindo).

Results:

Three hundred consecutive surgeries were included: urology/gynecology (n=105), digestive surgery (n=83), oncology (n=66), ENT surgery (n=28), thoracic surgery (n=18). Median age and weight at surgery were 9.5 [interquartile range (IQR)=8.8] years and 31 [IQR=29.3] kg, respectively. Over one year, 65 (22%) children presented with ≥1 complication, with Clavien-Dindo ≥III in 14/300 (5%) children at ≤30 days, 7/300 (2%) at 30-90 days, and 12/300 (4%) at >90 days. Perioperative transfusion was necessary in 15 (5%) children, mostly oncological (n=8). Eight (3%) robotic malfunctions were noted, one leading to conversion (laparotomy). Overall conversion rate was 4%. ASA ≥3, weight ≤15 kg, and surgical oncology did not significantly increase the conversion rate, complications, or intraoperative adverse events (ClassIntra ≥2). ASA score was significantly higher in children with complications (Clavien-Dindo ≥III) than without (p=0.01). Median hospital stay was 2 [IQR=3] days. Three children died after a median follow-up of 20 [IQR=16] months.

Conclusions:

RALS is safe, even in the most vulnerable children with a wide scope of indications, age, and weight. Robot-specific complications or malfunctions are scarce.
Settlement cue selectivity by larvae of the destructive crown-of-thorns starfish
Authors: Doll Peter C. , Uthicke Sven , Caballes Ciemon F. , Diaz-Pulido Guillermo , Abdul Wahab Muhammad A. , Lang Bethan J. , Jeong So Young , Pratchett Morgan S.
Published: January 2023

Population irruptions of crown-of-thorns starfish (COTS) cause extensive degradation of coral reefs, threatening the structure and function of these important ecosystems. For population irruptions to initiate and spread, large numbers of planktonic larvae have to successfully transition into their benthic life-history stage (i.e. settlement), whereby larval behaviour and the presence of settlement cues may shape spatial patterns of recruitment and adult densities. Our results demonstrate that a wide range of coralline algae species induce COTS larvae to settle; however, the capacity to promote settlement success varied manyfold among algal species, ranging from greater than 90% in
Melyvonnea
cf.
madagascariensis
to less than 2% in
Lithophyllum
cf.
kotschyanum
and two
Porolithon
species at 24 h. Because many coralline algae species that promote high settlement success are prevalent in shallow reef habitats, our findings challenge the hypothesis that COTS larvae predominantly settle in deep water. Considering both larval behaviour and algal ecology, this study highlights the ecological significance of coralline algae communities in driving recruitment patterns of COTS. More specifically, the local abundance of highly inductive coralline algae (especially,
Melyvonnea
cf.
madagascariensis
) may explain some of the marked spatial heterogeneity of COTS populations and the incidence of population irruptions.
Larger genomes show improved buffering of adult fitness against environmental stress in seed beetles
Authors: Boman Jesper , Arnqvist Göran
Published: January 2023

Our general understanding of the evolution of genome size (GS) is incomplete, and it has long been clear that GS does not reflect organismal complexity. Here, we assess the hypothesis that larger genomes may allow organisms to better cope with environmental variation. It is, for example, possible that genome expansion due to proliferation of transposable elements or gene duplications may affect the ability to regulate and fine-tune transcriptional profiles. We used 18 populations of the seed beetle
Callosobruchus maculatus
, which differ in GS by up to 4.5%, and exposed adults and juveniles to environmental stress in a series of experiments where stage-specific fitness was assayed. We found that populations with larger genomes were indeed better buffered against environmental stress for adult, but not for juvenile, fitness. The genetic correlation across populations between GS and canalization of adult fitness is consistent with a role for natural selection in the evolution of GS.
Context-dependent representation of within- and between-model uncertainty: aggregating probabilistic predictions in infectious disease epidemiology
Authors: Howerton Emily , Runge Michael C. , Bogich Tiffany L. , Borchering Rebecca K. , Inamine Hidetoshi , Lessler Justin , Mullany Luke C. , Probert William J. M. , Smith Claire P. , Truelove Shaun , Viboud Cécile , Shea Katriona
Published: January 2023

Probabilistic predictions support public health planning and decision making, especially in infectious disease emergencies. Aggregating outputs from multiple models yields more robust predictions of outcomes and associated uncertainty. While the selection of an aggregation method can be guided by retrospective performance evaluations, this is not always possible. For example, if predictions are conditional on assumptions about how the future will unfold (e.g. possible interventions), these assumptions may never materialize, precluding any direct comparison between predictions and observations. Here, we summarize literature on aggregating probabilistic predictions, illustrate various methods for infectious disease predictions via simulation, and present a strategy for choosing an aggregation method when empirical validation cannot be used. We focus on the linear opinion pool (LOP) and Vincent average, common methods that make different assumptions about between-prediction uncertainty. We contend that assumptions of the aggregation method should align with a hypothesis about how uncertainty is expressed within and between predictions from different sources. The LOP assumes that between-prediction uncertainty is meaningful and should be retained, while the Vincent average assumes that between-prediction uncertainty is akin to sampling error and should not be preserved. We provide an R package for implementation. Given the rising importance of multi-model infectious disease hubs, our work provides useful guidance on aggregation and a deeper understanding of the benefits and risks of different approaches.
A coarse-grained molecular dynamics investigation of the role of mineral arrangement on the mechanical properties of mineralized collagen fibrils
Authors: Tavakol Mahdi , Vaughan Ted J.
Published: January 2023

Mineralized collagen fibrils (MCFs) comprise collagen molecules and hydroxyapatite (HAp) crystals and are considered universal building blocks of bone tissue, across different bone types and species. In this study, we developed a coarse-grained molecular dynamics (CGMD) framework to investigate the role of mineral arrangement on the load-deformation behaviour of MCFs. Despite the common belief that the collagen molecules are responsible for flexibility and HAp minerals are responsible for stiffness, our results showed that the mineral phase was responsible for limiting collagen sliding in the large deformation regime, which helped the collagen molecules themselves undergo high tensile loading, providing a substantial contribution to the ultimate tensile strength of MCFs. This study also highlights different roles for the mineralized and non-mineralized protofibrils within the MCF, with the mineralized groups being primarily responsible for load carrying due to the presence of the mineral phase, while the non-mineralized groups are responsible for crack deflection. These results provide novel insight into the load-deformation behaviour of MCFs and highlight the intricate role that both collagen and mineral components have in dictating higher scale bone biomechanics.
Prosthetic valve endocarditis due to Candida parapsilosis – a rare case report
Authors: Sharma Shivang , Samantaray Subhashree , Kumar Deepak , Meena Durga Shankar , Chaudhary Rahul , Jain Vidhi , Bohra Gopal Krishana , Garg Mahendra Kumar
Published: January 2023

Fungal endocarditis is a rare and fatal condition, most frequently caused by species of the genera Candida and Aspergillus. Fever and changing heart murmur are the most common clinical manifestations. The diagnosis of fungal endocarditis is challenging, with prosthetic valve endocarditis being extremely difficult to diagnose. The optimal management of the condition still remains debatable. We present a case of prosthetic valve endocarditis caused by Candida parapsilosis, managed empirically with liposomal amphotericin B, which was later shifted to combination therapy with high-dose echinocandin and fluconazole, but had a fatal outcome because the patient could not undergo timely surgical intervention. Treating C. parapsilosis endocarditis cases is difficult because of their biofilm production on native and prosthetic heart valves. A combined approach consisting of a high index of clinical suspicion, early diagnosis using serological markers followed by culture or PCR and prompt initiation of appropriate antifungals may aid in improving outcomes.
COVID-19 isolation and quarantine orders in Berlin-Reinickendorf (Germany): How many, how long and to whom?
Authors: Schumacher Jakob , Kühne Lisa , Brüssermann Sophia , Geisler Benjamin , Jäckle Sonja
Published: January 2023

Isolating COVID-19 cases and quarantining their close contacts can prevent COVID-19 transmissions but also inflict harm. We analysed isolation and quarantine orders by the local public health agency in Berlin-Reinickendorf (Germany) and their dependence on the recommendations by the Robert Koch Institute, the national public health institute. Between 3 March 2020 and 18 December 2021 the local public health agency ordered 24603 isolations and 45014 quarantines (mean contacts per case 1.9). More days of quarantine per 100 inhabitants were ordered for children than for adults: 4.1 for children aged 0-6, 5.2 for children aged 7-17, 0.9 for adults aged 18-64 and 0.3 for elderly aged 65-110. The mean duration for isolation orders was 10.2 and for quarantine orders 8.2 days. We calculated a delay of 4 days between contact and quarantine order. 3484 of contact persons were in quarantine when they developed an infection. Our study quantifies isolation and quarantine orders, shows that children had been ordered to quarantine more than adults and that there were fewer school days lost to isolation or quarantine as compared to school closures. Our results indicate that the recommendations of the Robert Koch Institute had an influence on isolation and quarantine duration as well as contact identification and that the local public health agency was not able to provide rigorous contact tracing, as the mean number of contacts was lower than expected.
Blood flow restriction resistance training as an alternative to resistance training alone to improve strength in elderly: a systematic review with meta-analysis
Authors: Silveira Mallmann André Luiz , dos Santos Leonardo Peterson , Doria Lucas Denardi , Ferreira Luis Fernando , Ramis Thiago Rozales , da Rosa Luís Henrique Telles
Published: January 2023

The purpose of this research was to perform a systematic review with meta-analysis to compare the effects of resistance training with blood flow restriction (BFR) to the effects of non-training (CON) and traditional RT on strength in elderly people. This was a systematic review with meta-analysis of randomized clinical trials (RCTs), published in English, from inception to 2022, conducted using MEDLINE (PubMed), EMBASE, Web of Science and Cochrane Library. The methodological quality was assessed using GRADE protocol. The risk of bias was assessed using RoB2 software. Standardized mean differences (SMD), mean difference, were pooled using a random-effects model. A p < 0.05 was considered statistically significant. Eight RCT’s were included. We found no significant differences in the effects between BFR and RT (SMD = -0.18 [-0.56 to 0.19]; p = 0.34; I2= 12%). Also, evidence from our research shows that the effect of BFR is better than non-training (CON) for strengthening in older adults (SMD = 0.63 [0.24 to 1.01]; p = 0.001; I2= 11%). Our primary findings show that training with BFR may be an alternative methodology of training for the elderly and this training strategy may be interesting for health professionals working with elderly people with low tolerance to high intensity RT.
Is lifestyle coaching a potential cost-effective intervention to address the backlog for mental health counselling? A Rapid Review
Authors: Makanjuola Abraham , Granger Rachel , Pisavadia Kalpa , Edwards Rhiannon Tudor
Published: January 2023

Aim

The aim of this rapid review was to investigate whether lifestyle coaching could provide a cost-effective alternative to counselling for the UK National Health Service (NHS) treatment of common mental health conditions such as stress, anxiety and depression.

Methods

A rapid review approach was used to determine the evidence of health economics evaluations in the field of mental health services. A literature search of PubMed, CINAHL, Cochrane Library, ASSIA, PsycINFO and MEDLINE produced 2807 articles. We removed 778 duplicates, and 2029 study articles remained. Two reviewers screened titles and abstracts (RG and KP), and 37 papers met the inclusion criteria of this review. Following a full-text screening, a further 27 papers were excluded due to lack of relevance. Study designs which did not include economic evaluations (n=15) or did not include an evaluation treatment of mental health conditions with talking therapies (n=15) did not meet the inclusion criteria. Ten papers were included in the final rapid review.

Results

The database search yielded study articles which focused on the cost-effectiveness of counselling and other talking therapies such as Cognitive Behavioural Therapy (CBT). No literature was found to determine the cost-effectiveness, or effectiveness of lifestyle coaching. Due to a lack of economic evaluations, this review could not determine the potential cost-effectiveness of lifestyle coaching as a means of addressing the backlog for mental health support such as counselling in the NHS.

Conclusion

This review highlights the research gap in assessing the cost-effectiveness of lifestyle coaching for treating common mental health disorders. The proposed next step is to evaluate the effectiveness and cost-effectiveness of lifestyle coaching versus current treatment as usual (counselling) by using a feasibility randomised control trial.

Paper type

A rapid review

Article summary

Strengths and limitations of this study

This rapid review found a range of different economic evaluations of mental health interventions for common mental health issues.

All of the study articles found were moderate to high quality, some of the included study articles met all of the checklist criteria.

This rapid review found no evidence from a UK study setting. However, all study articles came from OECD countries that share similar legal structures and policies with comparable populations.

Despite being mentioned in a number of studies, it is unclear what treatment as usual refers to, and is perhaps not as usual as the studies suggest.
Systematic Review Association between Endotype of Prematurity and Mortality: A Systematic Review, Meta-analysis and Meta-regression
Authors: Hundscheid Tamara M , Villamor-Martinez Eduardo , Villamor Eduardo
Published: January 2023

Introduction

Preterm birth represents the leading cause of neonatal mortality. Pathophysiological pathways, or endotypes, leading to prematurity can be clustered into infection/inflammation and dysfunctional placentation. We aimed to perform a systematic review and meta-analysis exploring the association between these endotypes and risk of mortality during first hospital admission.

Methods

PROSPERO ID: CRD42020184843. PubMed and Embase were searched for observational studies examining infants with gestational age (GA) ≤34 weeks. Chorioamnionitis represented the infectious-inflammatory endotype, while dysfunctional placentation proxies were hypertensive disorders of pregnancy (HDP) and small for GA (SGA)/intrauterine growth restriction (IUGR). A random-effects model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Heterogeneity was studied using random-effects meta-regression analysis.

Results

Of 4322 potentially relevant studies, 150 (612,580 infants) were included. Meta-analysis showed a positive mortality odds for chorioamnionitis (OR 1.43, 95% CI 1.25-1.62) and SGA/IUGR (OR 1.68, 95% CI 1.38-2.04), but a negative mortality odds for HDP (OR 0.74, 95% CI 0.64-0.86). Chorioamnionitis was associated with a lower GA, while HDP and SGA/IUGR were associated with a higher GA. Meta-regression showed a significant correlation between these differences in GA and mortality odds.

Discussion/Conclusion

Our data suggest that the infectious/inflammatory endotype of prematurity has a greater overall impact on mortality risk as it is the most frequent endotype in the lower GAs. However, when the endotype of placental dysfunction is severe enough to induce growth restriction, it is strongly associated with higher mortality rates even though newborns are more mature.
Comparison of outcomes of Long versus Short Cephalomedullary nails for the fixation of intertrochanteric femur fractures: A Protocol for Systematic Review and Meta-analysis
Authors: Rajnish Rajesh Kumar , Srivastava Amit , Kumar Prasoon , Yadav Sandeep Kumar , Sharma Siddhartha , Haq Rehan Ul , Aggarwal Aditya Nath
Published: January 2023

Background

The incidence of intertrochanteric femur fracture (IFF) in the elderly has increased with increased life expectancy globally. These fractures require surgeries at the earliest to bring them out of bed and minimize the complications of recumbency, like decubitus ulcers, decreased cardiopulmonary reserves, and thromboembolic events. Dynamic hip screws and Cephalomedullary nails (CMN) are both considered adequate for the internal fixation of the stable IFF with comparable stability and outcomes. However, CMNs are considered to have better results in unstable IFF fixation.

Objective

To compare the outcomes of internal fixation of short CMN versus long CMN of IFF in the elderly by analyzing the evidence from the current literature.

Methods

A systematic review and meta-analysis will be performed in accordance with the PRISMA guidelines. A primary search of Medline, Embase, Scopus, and Cochrane Library databases will be conducted using a pre-defined search strategy. The studies of any design in the English language will be included, which have compared the outcomes of the internal fixation of short CMN versus long CMN of the IFF and reported at least one primary or secondary outcome of interest.

Studies that did not compare the outcomes of the internal fixation of short CMN versus long CMN of the IFF, conference abstracts, posters, case reports, book chapters, technical tips, review articles, biomechanical studies, cadaveric studies, and the articles not in the English language will be excluded.

Both qualitative and quantitative analyses will be performed. A qualitative analysis will be performed using appropriate tables and diagrams. Wherever feasible, quantitative analysis will be done with the appropriate software. The risk-of-bias assessment for non-randomized comparative studies will be done using the MINORS tool, and the Cochrane Collaboration’s risk-of-bias tool will be used for randomized control trials (RCT).
A scoping review on the associations and potential pathways between malnutrition and measles
Authors: Tran Isabelle CT , Gregory Christopher , O’Connor Patrick , Imohe Annette , Do Lien Anh Ha , Suchdev Parminder S
Published: January 2023

Amid a measles resurgence worldwide, many affected regions also find themselves in circumstances of conflict, humanitarian or political crises, climate extremes, ongoing pandemic challenges, income inequality and economic downturns. Those contextual factors have driven increases in worldwide undernourishment over the past year. The overlap and frequent occurrence of those socio-structural determinants in fragile geographies is worrying as a synergistic relationship between measles and malnutrition has been reported. A scoping review was conducted to map current evidence and identify research gaps on the association between malnutrition and measles.

Sixty-seven studies were retained following a search of multiple databases, snowballing and consultations with experts. Studies reported on a measure of association, a relationship, or potential mechanisms behind the link between malnutrition and measles.

Overall, there was evidence of a positive correlation between undernutrition and reported measles incidence and mortality. All studies reviewed found an association between vitamin A deficiency and increased likelihood of incident measles, measles-related complications and measles-related deaths. Available evidence also suggested that therapeutic vitamin A can significantly reduce the odds of measles-related mortality, and preventative vitamin A can reduce reported measles incidence. Little data shed light on potential pathways behind malnutrition and measles. Inconsistent variable definitions (i.e. malnutrition and measles cases) across studies precluded calculating a cumulative effect size, and findings may be impacted by uncontrolled confounding factors.

This scoping review reinforces the hypothesis of a synergistic relationship between measles and malnutrition and highlights the need for an integrated approach to the delivery of malnutrition interventions and measles prevention and control. In addition, further robust studies are needed to better define pathophysiological targets for interventions and allow for stronger inferences to policy making. Future research should also consider using a standardized approach to defining malnutrition and measles to ensure comparability of outcomes across studies.
Rational positioning of 3D printed micro-bricks to realize high-fidelity, multi-functional soft-hard interfaces
Authors: Saldívar M. C. , Salehi S. , Veeger R. P. E. , Fenu M. , Cantamessa A. , Klimopoulou M. , Talò G. , Moretti M. , Lopa S. , Ruffoni D. , van Osch G.J.V.M. , Fratila-Apachitei L. E. , Doubrovski E. L. , Mirzaali M. J. , Zadpoor A. A.
Published: January 2023

Abstract

Living organisms have developed design principles, such as functional gradients (FGs), to interface hard materials with soft ones (e.g., bone and tendon). Mimicking such design principles can address the challenges faced when developing engineered constructs with soft-hard interfaces. To date, implementing these FG design principles has been primarily performed by varying the ratio of the hard phase to that of the soft phase. Such design approaches, however, lead to inaccurate mechanical properties within the transition zone. That is due to the highly nonlinear relationship between the material distribution at the microscale and the macroscale mechanical properties. Here, we 3D print micro-bricks from either a soft or a hard phase and study the nonlinear relationship between their arrangements within the transition zone and the resulting macroscale properties. We carry out experiments at the micro- and macroscales as well as finite element simulations at both scales. Based on the obtained results, we develop a co-continuous power-law model relating the arrangement of the micro-bricks to the local mechanical properties of the micro-brick composites. We then use this model to rationally design FGs at the individual micro-brick level and create two types of biomimetic soft-hard constructs, including a specimen modeling bone-ligament junctions in the knee and another modeling the nucleus pulposus-annulus fibrosus interface in intervertebral discs. We show that the implemented FGs drastically enhance the stiffness, strength, and toughness of both types of specimens as compared to non-graded designs. Furthermore, we hypothesize that our soft-hard FGs regulate the behavior of murine preosteoblasts and primary human bone marrow-derived mesenchymal stromal cells (hBMSCc). We culture those cells to confirm the effects of soft-hard interfaces on cell morphology as well as on regulating the expression of focal adhesion kinase, subcellular localization, and YAP nuclear translocation of hBMSCs. Taken together, our results pave the way for the rational design of soft-hard interfaces at the micro-brick level and (biomedical) applications of such designs.
Wastewater-based surveillance can be used to model COVID-19-associated workforce absenteeism
Authors: Acosta Nicole , Dai Xiaotian , Bautista Maria A. , Waddell Barbara J. , Lee Jangwoo , Du Kristine , McCalder Janine , Pradhan Puja , Papparis Chloe , Lu Xuewen , Chekouo Thierry , Krusina Alexander , Southern Danielle , Williamson Tyler , Clark Rhonda G. , Patterson Raymond A. , Westlund Paul , Meddings Jon , Ruecker Norma , Lammiman Christopher , Duerr Coby , Achari Gopal , Hrudey Steve E. , Lee Bonita E. , Pang Xiaoli , Frankowsk Kevin , Hubert Casey R.J. , Parkins Michael D.
Published: January 2023

Wastewater-based surveillance (WBS) is a powerful tool for understanding community COVID-19 disease burden and informing public health policy. The potential of WBS for understanding COVID-19’s impact in non-healthcare settings has not been explored to the same degree. Here we examined how SARS-CoV-2 measured from municipal wastewater treatment plants (WWTPs) correlates with local workforce absenteeism. SARS-CoV-2 RNA N1 and N2 were quantified three times per week by RT-qPCR in samples collected at three WWTPs servicing Calgary and surrounding areas, Canada (1.3 million residents) between June 2020 and March 2022. Wastewater trends were compared to workforce absenteeism using data from the largest employer in the city (>15,000 staff). Absences were classified as being COVID-19-related, COVID-19-confirmed, and unrelated to COVID-19. Poisson regression was performed to generate a prediction model for COVID-19 absenteeism based on wastewater data. SARS-CoV-2 RNA was detected in 95.5% (85/89) of weeks assessed. During this period 6592 COVID-19-related absences (1896 confirmed) and 4,524 unrelated absences COVID-19 cases were recorded. Employee absences significantly increased as wastewater signal increased through the pandemic’s waves. Strong correlations between COVID-19-confirmed absences and wastewater SARS-CoV-2 signals (N1 gene: r=0.824, p<0.0001 and N2 gene: r=0.826, p<0.0001) were observed. Linear regression with adjusted R2-value demonstrated a robust association (adjusted R2=0.783), when adjusted by 7 days, indicating wastewater provides a one-week leading signal. A generalized linear regression using a Poisson distribution was performed to predict COVID-19-confirmed absences out of the total number of absent employees using wastewater data as a leading indicator (P<0.0001). We also assessed the variation of predictions when the regression model was applied to new data, with the predicted values and corresponding confidence intervals closely tracking actual absenteeism data. Wastewater-based surveillance has the potential to be used by employers to anticipate workforce requirements and optimize human resource allocation in response to trackable respiratory illnesses like COVID-19.

Highlights

WBS is a useful strategy for monitoring infectious diseases in workers

SARS-CoV-2 RNA in wastewater correlated with workforce absenteeism

Workplace absenteeism secondary to COVID-19 can be predicted using WBS

WBS can be used by employers to anticipate and mitigate work force absenteeism

Graphical abstract
Joint Temporal Patterns By Integrating Diet and Physical Activity
Authors: Guo Jiaqi , Lin Luotao , Aqeel Marah M. , Gelfand Saul B. , Eicher-Miller Heather A. , Bhadra Anindya , Hennessy Erin , Richards Elizabeth A. , Delp Edward J.
Published: January 2023

Both diet and physical activity are associated with obesity and chronic diseases such as diabetes and metabolic syndrome. Early efforts in connecting dietary and physical activity behaviors to generate patterns rarely considered the use of time. In this paper, we propose a distance-based cluster analysis approach to find joint temporal diet and physical activity patterns among U.S. adults ages 20-65. Dynamic Time Warping (DTW) generalized to multi-dimensions is combined with commonly used clustering methods to generate unbiased partitioning of the National Health and Nutrition Examination Survey 2003-2006 (NHANES) dataset. The clustering results are evaluated using visualization of the clusters, the Silhouette Index, and the associations between clusters and health status indicators based on multivariate regression models. Our experiments indicate that the integration of diet, physical activity, and time has the potential to discover joint temporal patterns with association to health.
Real-world effectiveness of Azvudine in hospitalized patients with COVID-19: a retrospective cohort study
Authors: Shen Minxue , Xiao Chenggen , Sun Yuming , Li Daishi , Wu Ping , Jin Liping , Wu Qingrong , Dian Yating , Meng Yu , Zeng Furong , Chen Xiang , Deng Guangtong
Published: January 2023

Current guidelines prioritize the use of the Azvudine in coronavirus disease 2019 (COVID-19) patients. However, the clinical effectiveness of Azvudine in real-world studies was lacking, despite the clinical trials showed shorter time of nucleic acid negative conversion. To evaluate the clinical effectiveness following Azvudine treatment in hospitalized COVID-19 patients, we identified 1505 hospitalized COVID-19 patients during the study period, with a follow-up of up to 29 days. After exclusions and propensity score matching, we included 226 Azvudine recipients and 226 matched controls. The lower crude incidence rate of composite disease progression outcome (4.21 vs. 10.39 per 1000 person-days,P=0.041) and all-cause mortality (1.57 vs. 6.00 per 1000 person-days,P=0.027) were observed among Azvudine recipients compared with matched controls. The incidence rates of initiation of invasive mechanical ventilation were also statistically different between the groups according to the log-rank tests (P=0.020). Azvudine treatment was associated with significantly lower risks of composite disease progression outcome (hazard ratio [HR]: 0.43; 95% confidence interval [CI]: 0.18 to 0.99) and all-cause death (HR: 0.26; 95% CI: 0.07 to 0.94) compared with matched controls. Subgroup analyses indicated robustness of the point estimates of HRs (ranged from 0.14 to 0.84). Notably, male Azvudine recipients had a stronger effectiveness than female recipients with respect to both composite outcome and all-cause death. These findings suggest that Azvudine treatment showed substantial clinical benefits in hospitalized COVID-19 patients, and should be considered for use in this population of patients.
DOPA residues endow collagen with radical scavenging capacity
Authors: Kurth Markus , Barayeu Uladzimir , Gharibi Hassan , Kuzhelev Andrei , Riedmiller Kai , Zilke Jennifer , Noack Kasimir , Denysenkov Vasyl , Kappl Reinhard , Prisner Thomas F. , Zubarev Roman A. , Dick Tobias P. , Gräter Frauke
Published: January 2023

Here we uncover collagen, the main structural protein of all connective tissues, as a redox-active material. We identify dihydroxyphenylalanine (DOPA) residues, post-translational oxidation products of tyrosine residues, to be common in collagen derived from different connective tissues. We observe that these DOPA residues endow collagen with substantial radical scavenging capacity. When reducing radicals, DOPA residues work as redox relay: they convert to the quinone and generate hydrogen peroxide. In this dual function, DOPA outcompetes its amino acid precursors and ascorbic acid. Our results establish DOPA residues as redox-active side chains of collagens, probably protecting connective tissues against radicals formed under mechanical stress and/or inflammation.
Lung infection byP. aeruginosainduces neuroinflammation and blood-brain barrier dysfunction in mice
Authors: Villalba Nuria , Ma Yonggang , Gahan Sarah A. , Joly-Amado Aurelie , Spence Sam , Yang Xiaoyuan , Nash Kevin , Yuan Sarah Y.
Published: January 2023

Background

Severe lung infection can lead to brain dysfunction and neurobehavioral disorders. The mechanisms that regulate the lung-brain axis of inflammatory response to respiratory infection are incompletely understood. This study examined the effects of lung infection causing systemic and neuroinflammation as a potential mechanism contributing to blood-brain barrier (BBB) leakage and behavioral impairment.

Methods

Pneumonia was induced in adult C57BL/6 mice by intratracheal inoculation ofPseudomonas aeruginosa(PA). Solute extravasation, histology, immunofluorescence, RT-PCR, multiphoton imaging and neurological testing were performed in this study.

Results

Lung infection caused alveolar-capillary barrier injury as indicated by leakage of plasma proteins across pulmonary microvessels and histopathological characteristics of pulmonary edema (alveolar wall thickening, microvessel congestion, and neutrophil infiltration). PA also caused significant BBB dysfunction characterized by leakage of different sized molecules across cerebral microvessels and a decreased expression of cell-cell junctions (VE-cadherin, claudin-5) in the brain. BBB leakage peaked at 24 hours and lasted for 7 days post-inoculation. Additionally, mice with lung infection displayed hyperlocomotion and anxiety-like behaviors. To test whether cerebral dysfunction was caused by PA directly or indirectly, we measured bacterial load in multiple organs. While PA loads were detected in the lungs up to 7 days post-inoculation, bacteria were not detected in the brain as evidenced by negative cerebral spinal fluid (CSF) cultures and lack of distribution in different brain regions or isolated cerebral microvessels. However, mice with PA lung infection demonstrated increased mRNA expression in the brain of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), chemokines (CXCL-1, CXCL-2) and adhesion molecules (VCAM-1 and ICAM-1) along with CD11b+ cell recruitment, corresponding to their increased blood levels of white cells (polymorphonuclear cells) and cytokines. To confirm the direct effect of cytokines on endothelial permeability, we measured cell-cell adhesive barrier resistance and junction morphology in mouse brain microvascular endothelial cell monolayers, where administration of IL-1β induced a significant reduction of barrier function coupled with tight junction (TJ) diffusion and disorganization. Combined treatment with IL-1β and TNFα augmented the barrier injury.

Conclusions

These results suggest that lung bacterial infection causes cerebral microvascular leakage and neuroinflammation via a mechanism involving cytokine-induced BBB injury.
DRACC1, a major postsynaptic protein, regulates the condensation of postsynaptic proteins via liquid-liquid phase separation
Authors: Kaizuka Takeshi , Hirouchi Taisei , Saneyoshi Takeo , Hayashi Yasunori , Takumi Toru
Published: January 2023

Numerous proteome analyses have been conducted on the postsynaptic density (PSD), a protein condensate beneath the postsynaptic membrane of excitatory synapses. Each has identified several hundred to thousands of proteins. While proteins with predictable functions have been well studied, functionally uncharacterized proteins are mostly overlooked. In this study, we perform a meta-analysis of the 35 PSD proteome datasets, including 5,869 proteins, identifying 97 uncharacterized proteins that appeared in multiple datasets. We focus on the top-ranked protein, FAM81A, renamed DRACC1. DRACC1 is expressed in forebrain neurons and enriched at the synapse. DRACC1 interacts with PSD proteins, including PSD-95, SynGAP, and NMDA receptors, and promotes liquid-liquid phase separation of those proteins. Consistently, the downregulation of DRACC1 in neurons causes a decrease in the size of PSD-95 puncta and the frequency of neuronal firing. Our results characterize DRACC1 as a novel synaptic protein facilitating the assembly of proteins within PSD. It also indicates the effectiveness of a meta-analytic approach of existing proteome datasets in identifying uncharacterized proteins.
3Din vitromodeling of the exocrine pancreatic unit using tomographic volumetric bioprinting
Authors: Sgarminato Viola , Madrid-Wolff Jorge , Boniface Antoine , Ciardelli Gianluca , Tonda-Turo Chiara , Moser Christophe
Published: January 2023

1.

Pancreatic ductal adenocarcinoma (PDAC) is the most frequent type of pancreatic cancer, one of the leading causes of cancer-related deaths worldwide. The first lesions associated with PDAC occur within the functional units of exocrine pancreas. The crosstalk between PDAC cells and stromal cells plays a key role in tumor progression. Thus, in vitro, fully human models of the pancreatic cancer microenvironment are needed to foster the development of new, more effective therapies. However, it is challenging to make these models anatomically and functionally relevant. Here, we used tomographic volumetric bioprinting, a novel method to fabricate three-dimensional cell-laden constructs, to produce a portion of the complex convoluted exocrine pancreasin vitro. Human fibroblast-laden gelatin methacrylate-based pancreatic models were processed to reassemble the tubuloacinar structures of the exocrine pancreas and, then human pancreatic ductal epithelial (HPDE) cells overexpressing the KRAS oncogene (HPDE-KRAS) were seeded in the acinar lumen to reproduce the pathological exocrine pancreatic tissue. The growth and organization of HPDE cells within the structure was evaluated and the formation of a thin epithelium which covered the acini inner surfaces in a physiological way inside the 3D model was successfully demonstrated. Interestingly, immunofluorescence assays revealed a significantly higher expressions of alpha smooth muscle actin (α-SMA) vs. actin in the fibroblasts co-cultured with cancerous than with wild-type HPDE cells. Moreover, α-SMA expression increased with time, and it was found to be higher in fibroblasts that laid closer to HPDE cells than in those laying deeper into the model. Increased levels of interleukin (IL)-6 were also quantified in supernatants from co-cultures of stromal and HPDE-KRAS cells. These findings correlate with inflamed tumor-associated fibroblast behavior, thus being relevant biomarkers to monitor the early progression of the disease and to target drug efficacy.

To our knowledge, this is the first demonstration of a 3D bioprinted portion of pancreas that recapitulates its true 3-dimensional microanatomy, and which shows tumor triggered inflammation.
Failed down-regulation of PI3K signaling makes autoreactive B cells receptive to bystander T cell help
Authors: Fiske Brigita E. , Getahun Andrew
Published: January 2023

The role of T cell help in autoantibody responses is not well understood. Since tolerance mechanisms govern both T and B cell responses, one might predict that both T cell tolerance and B cell tolerance must be defeated in autoantibody responses requiring T cell help. To define whether autoreactive B cells depend on T cells to generate autoantibody responses, we studied the role of T cells in autoantibody responses resulting from acute cell-specific deletion of regulatory phosphatases. Ars/A1 B cells are DNA-reactive and require continuous inhibitory signaling by the tyrosine phosphatase SHP-1 and the inositol phosphatases SHIP-1 and PTEN to maintain unresponsiveness. Acute B cell-restricted deletion of any of these phosphatases results in an autoantibody response. Here we show that CD40-CD40L interactions are required to support autoantibody responses of B cells whose anergy has been compromised. If the B cell-intrinsic driver of loss of tolerance is failed negative regulation of PI3K signaling, bystander T cells provide sufficient CD40-mediated signal 2 to support an autoantibody response. However, while autoantibody responses driven by acute B cell-targeted deletion of SHP-1 also require T cells, bystander T cell help does not suffice. These results demonstrate that upregulation of PI3K signaling in autoreactive B cells, recapitulating the effect of multiple autoimmunity risk alleles, promotes autoantibody responses both by increasing B cells’ cooperation with non-cognate T cell help, as well as by altering BCR signaling. Receptiveness to bystander T cell help enables autoreactive B cells to circumvent the fail-safe of T cell tolerance.

Significance

Phosphatase suppression of PI3K signaling is an important mechanism by which peripheral autoreactive B cells are kept in an unresponsive/anergic state. Loss of this suppression, due to genetic alleles that confer risk of autoimmunity, often occurs in autoreactive B cells of individuals who develop autoimmune disease. Here we demonstrate that de-repression of PI3K signaling promotes autoantibody responses of a DNA-reactive B cell clone by relaxing dependence of autoantibody responses on T cell-derived helper signals. These results suggest that impaired regulation of PI3K signaling can promote autoantibody responses in two ways: by restoring antigen receptor signaling and by enabling autoreactive B cells to circumvent restrictions imposed by T cell tolerance mechanisms.
Explain-seq: an end-to-end pipeline from training to interpretation of sequence-based deep learning models
Authors: Zhao Nanxiang , Wang Shuze , Huang Qianhui , Dong Shengcheng , Boyle Alan P.
Published: January 2023

Interpreting predictive machine learning models to derive biological knowledge is the ultimate goal of developing models in the era of genomic data exploding. Recently, sequence-based deep learning models have greatly outperformed other machine learning models such as SVM in genome-wide prediction tasks. However, deep learning models, which are black-box models, are challenging to interpret their predictions. Here we represented an end-to-end computational pipeline, Explain-seq, to automate the process of developing and interpreting deep learning models in the context of genomics. Explain-seq takes input as genomic sequences and outputs predictive motifs derived from the model trained on sequences. We demonstrated Explain-seq with a public STARR-seq dataset of the A549 human lung cancer cell line released by ENCODE. We found our deep learning model outperformed gkm-SVM model in predicting A549 enhancer activities. By interpreting our well-performed model, we identified 47 TF motifs matched with known TF PWMs, including ZEB1, SP1, YY1, and INSM1. They are associated with epithelial-mesenchymal transition and lung cancer proliferation and metagenesis. In addition, there were motifs that were not matched in the JASPAR database and may be considered asde novoenhancer motifs in the A549 cell line.

Availability

https://github.com/nsamzhao/Explain-seq

Contact

apboyle@umich.edu

Supplementary information

Supplementary data are available as attachment.