bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for Validity and Reliability, and Development of Performance Standards and Cut-Scores for Job-Related Tests of Physical Aptitude for Structural Firefighters
Authors: Scarlett Michael P. , Rogers W. Todd , Adams Eric M. , Dreger Randy W. , Petersen Stewart R.
Published: November 2021

Objective:

This multi-part study aimed to revise an existing battery of physical aptitude tests for firefighter applicants. Test validity and reliability were evaluated and performance thresholds were determined.

Methods:

In Part I, 49 structural firefighters rated the similarity between the physical demands of the tests and corresponding work activities. In Part II, 23 participants completed the tests on 3 separate days. In Part III, cut-scores were determined using the Bookmark method by an expert panel of 25 firefighter supervisors.

Results:

Analysis revealed high levels of validity and reliability. The expert panel provided invaluable direction through a combination of independent and group work, leading to consensus on acceptable completion times.

Conclusion:

Rigorous processes established scientific credibility for the revised battery of tests. Expert knowledge from firefighter supervisors contributed to determining cut-scores following established scientific methods.
Health and Safety Practices and Perceptions of COVID-19 in Long-Haul Truck Drivers
Authors: Crizzle Alexander M.
Published: November 2021

Objective:

To examine long-haul truck drivers (LHTD) perceptions of COVID-19 and their use of health and safety practices.

Methods:

146 LHTD completed an online survey to collect data on their experiences with COVID-19. Data were analyzed using descriptive and inferential statistics, and thematic analysis for open-ended responses.

Results:

LHTD were aged from 22 to 79 years (mean age 48.1 ± 11.8); 82.2% were men. Almost half of the sample were not concerned about COVID-19. Those not concerned were significantly less likely to employ health and safety practices (eg, wearing masks, social distancing), were less educated and healthier. They also perceived COVID-19 to not be real or a serious threat to their health.

Conclusions:

Tailored education approaches are needed to provide evidence-based data on COVID-19 risks and complications.
The diagnostic journey in adults with hypermobile Ehlers–Danlos syndrome and hypermobility spectrum disorders
Authors: Anderson Linda K. , Lane Kari R.
Published: November 2021

Background:

Researchers have identified lengthy diagnosis delays in patients with hypermobile Ehlers–Danlos syndrome and hypermobility spectrum disorders (hEDS/HSD), but the reason for these delays is unclear.

Objective:

This review seeks to synthesize the existing qualitative research about hEDS/HSD to understand the reasons for diagnosis delay.

Data sources:

We searched PubMed, Scopus, CINAHL, Google Scholar, and Dissertations and Theses databases for all qualitative studies about hEDS/HSD that mentioned the diagnosis process. A total of 283 studies were retrieved, from which we identified 13 studies to include in this synthesis.

Conclusions:

The reviewers identified and organized diagnosis delay themes under four overarching categories: disease, patient, provider, and system. Disease factors included the nature of the symptoms and lack of a confirmatory test. Patient factors included psychological and emotional responses, seeing multiple providers, and receiving multiple diagnoses. Provider factors related to limited knowledge and attitudes. System factors included silo-based health care systems and bureaucratic barriers.

Implications for practice:

Diagnosis delays result from complex, overlapping, and interacting factors. Nurse practitioners have a critical role in improving care and reducing diagnosis delays in patients with hEDS/HSD. Further research is needed to understand the causes and consequences of diagnosis delays in hEDS/HSD.
Artificial Intelligence in the Diagnosis of Upper Gastrointestinal Diseases
Authors: Visaggi Pierfrancesco , de Bortoli Nicola , Barberio Brigida , Savarino Vincenzo , Oleas Roberto , Rosi Emma M. , Marchi Santino , Ribolsi Mentore , Savarino Edoardo
Published: November 2021

Artificial intelligence (AI) has enormous potential to support clinical routine workflows and therefore is gaining increasing popularity among medical professionals. In the field of gastroenterology, investigations on AI and computer-aided diagnosis (CAD) systems have mainly focused on the lower gastrointestinal (GI) tract. However, numerous CAD tools have been tested also in upper GI disorders showing encouraging results. The main application of AI in the upper GI tract is endoscopy; however, the need to analyze increasing loads of numerical and categorical data in short times has pushed researchers to investigate applications of AI systems in other upper GI settings, including gastroesophageal reflux disease, eosinophilic esophagitis, and motility disorders. AI and CAD systems will be increasingly incorporated into daily clinical practice in the coming years, thus at least basic notions will be soon required among physicians. For noninsiders, the working principles and potential of AI may be as fascinating as obscure. Accordingly, we reviewed systematic reviews, meta-analyses, randomized controlled trials, and original research articles regarding the performance of AI in the diagnosis of both malignant and benign esophageal and gastric diseases, also discussing essential characteristics of AI.
Belching
Authors: Rangan Vikram , Sheth Tia , Iturrino Johanna , Ballou Sarah , Nee Judy , Lembo Anthony
Published: November 2021

Purpose:

Belching is a common condition that frequently overlaps with other functional gastrointestinal disorders. While not associated with any increase in mortality, it is associated with impaired health-related quality of life. Management is challenging, as there are no pharmacologic therapies specifically targeted towards this disorder. This review covers pathogenesis, prevalence, and treatments for this condition, with specific emphasis on the evolving role of behavioral treatments in management.

Key Findings:

The diagnosis of gastric and supragastric belching can usually be made clinically, without the need for invasive testing. If necessary, multichannel intraluminal impedance and pH testing can provide a more definitive diagnosis and can also be used to estimate the frequency of gastric and supragastric belching episodes, which each have a distinct appearance on impedance tracing. Belching disorders are commonly associated with gastroesophageal reflux disease and functional disorders of the gastrointestinal tract. Supragastric belching is also associated with behavioral disorders like anxiety and obsessive-compulsive disorder. Speech therapy, cognitive-behavioral therapy, and diaphragmatic breathing are all interventions that have recently shown promise in the management of this challenging disorder.
The Impact of Medicare Health Insurance Coverage on Lung Cancer Screening
Authors: Sun Jiren , Perraillon Marcelo Coca , Myerson Rebecca
Published: November 2021

Background:

Annual lung cancer screening via low-dose computed tomography can reduce lung cancer mortality among high-risk adults by 20%; however, screening take-up remains low. Inadequate insurance coverage or access to care may be a barrier to screening.

Objective:

The objective of this study was to estimate the effect of nearly universal access to Medicare coverage on annual lung cancer screening.

Research Design:

A regression discontinuity design was used to estimate the causal effect of nearly universal access to Medicare at age 65. Data come from the 2017 to 2019 Behavioral Risk Factor Surveillance System in 28 states that adopted the optional module on lung cancer screening and lung cancer risk.

Subjects:

A total of 11,163 individuals at high risk for lung cancer just above and below age 65.

Measure:

Self-reported use of low-dose computed tomography to screen for lung cancer in the past 12 months.

Results:

A total of 10,951 people at high lung cancer risk (45.7% women, response rate=98.1%) reported lung cancer screening information. Nearly universal access to Medicare increased lung cancer screening by 16.2 percentage points among men (95% confidence interval: 2.4%–30.0%, P=0.02), compared with a baseline screening rate of 11.1% just younger than age 65. Women had a baseline screening rate of 18.2% and experienced no statistically significant change in screening (1.6 percentage point increase, 95% confidence interval: −19.8% to 23.0%, P=0.88).

Conclusions:

Gaining Medicare coverage at age 65 increased lung cancer screening take-up among men at high lung cancer risk. Lack of insurance or inadequate access to care hinders screening.
Quality and Safety in Healthcare, Part XCII
Authors: Harolds Jay A.
Published: November 2021

Six Sigma is a methodology to diminish variation and errors and improve efficiency, quality, value, and profit, using certain defined steps and statistical analysis. For existing products and services, the DMAIC (Define, Measure, Analyze, Improve, and Control) acronym is used to stand for its steps. For new products and services, the Design for Six Sigma methodology is used. The goal of Six Sigma is to reduce the number of defects to no more than 3.4 for every million opportunities.
Dual-Phase 18F-Florbetaben PET/CT
Authors: Rudolphi-Solero Teodoro , Triviño Ibáñez Eva María , Aroui Tarik , Navidad Rocío Hervás , Gómez-Río Manuel
Published: November 2021

Dual-phase amyloid PET is considered a useful protocol to study patients with cognitive impairment. Early-phase 18F-florbetaben PET/CT has been proposed as a surrogate of 18F-FDG PET/CT providing information related to regional brain perfusion. We report the case of a 61-year-old woman referred to the cognitive impairment unit for study, preliminary diagnosed as probable Alzheimer disease. The dual-phase 18F-florbetaben PET/CT was shown as the main finding, no uptake in the left anterior thalamus. Memory and language symptoms have been described as primary clinical features of anterior thalamic infarctions that could be confused with the main manifestations of Alzheimer disease.
Rare Presentation of Late Complications After Undiagnosed Perforated Appendicitis Mimicking Recurrent Endometrial Carcinoma on 18F-FDG PET/CT
Authors: Dejanovic Danijela , Elgaard Tenna , Loft Annika , Mosgaard Berit Jul
Published: November 2021

Acute appendicitis is one of the most common causes of acute abdominal pain. Undiagnosed or untreated appendicitis can lead to serious complications. The most frequent complication of acute appendicitis is perforation with subsequent formation of a localized periappendiceal abscess or diffuse bacterial peritonitis. Late occurring complications following undiagnosed appendix perforation can pose a diagnostic challenge due to uncharacteristic clinical and imaging presentation. Herein, we describe late findings of undiagnosed perforated appendicitis that on 18F-FDG PET/CT mimicked recurrent endometrial carcinoma disease in a 67-year-old woman.
Radiation Recall Pneumonitis on FDG PET/CT Triggered by COVID-19 Vaccination
Authors: Hughes Nicola M. , Hammer Mark M. , Awad Mark M. , Jacene Heather A.
Published: November 2021

A 67-year-old man with metastatic lung adenocarcinoma was initially treated with whole-brain radiotherapy for intracranial metastases, followed by chemotherapy and pembrolizumab. After completing 2 years of systemic therapy, the primary right lung lesion was biopsy-proven to have residual adenocarcinoma, which was then treated with radiation (6000 cGy in 15 fractions). Follow-up serial FDG PET/CT showed radiation fibrosis. Eighteen months after radiotherapy, the patient received 2 doses of an mRNA COVID-19 vaccine. FDG PET/CT performed 4 days following his second vaccine dose showed FDG-avid multistation lymphadenopathy and radiation recall pneumonitis, likely vaccination-induced and mimicking recurrent disease. This resolved spontaneously without therapy.
Topographic Anatomy of the Zygomatico-Orbital Artery
Authors: Lee Hye-In , Park Jung-Ah , Yeo In-Seung , Koh Ki-Seok , Song Wu-Chul
Published: November 2021

The zygomatico-orbital artery (ZOA) originating from the superficial temporal artery and supplying the lower temporal region superficially has been reported. Previous studies of this artery have used definitions that are too ambiguous for the results to be directly adapted to clinical practice, including since they have resulted in marked variations in the reported incidence ofthe artery. This study dissected 193 hemifaces of 123 fixed human cadavers aged 36 to 102 years (119 males and 74 females). The authors investigated the ZOA based on the following definition: (1) it originates from the superficial temporal artery, (2) it runs mostly above the zygomatic arch, and (3) it terminates below the superior border of the orbicularis oculi muscle. The incidence of the ZOA was 22.8% (44 cases of 193 sides), and its mean diameter was 1.1 mm. The meanvertical distances from the superior borderofthe zygomatic arch to the artery were 29.6, 17.8, and 2.9 mm at the jugale, zygion, and the origin of the ZOA, respectively. An accurate definition of the ZOA and accurate knowledge of its incidence and course could be important for clinicians to avoid unintentional complications in clinical practice.
Early metabolic support for critically ill trauma patients: A prospective randomized controlled trial
Authors: Stolarski Allan E. , Young Lorraine , Weinberg Janice , Kim Jiyoun , Lusczek Elizabeth , Remick Daniel G. , Bistrian Bruce , Burke Peter
Published: November 2021

BACKGROUND

There is a lack of consensus regarding the optimal nutritional support for trauma patients. We hypothesize that early postinjury metabolic support focusing on adequate protein would modify the metabolic signature and alter the inflammatory environment for critically ill trauma patients.

METHODS

We conducted a prospective randomized controlled pilot trial for adult patients admitted to the surgical intensive care unit following traumatic injury. Patients were randomized to receive early metabolic support (EMS) (peripheral amino acid infusions) or standard of care (enteral nutrition as soon as feasible). Routine laboratory assessments, nitrogen balance, cytokines, and metabolomic analyses were assessed at baseline and day 5 after intervention.

RESULTS

A total of 42 trauma patients were randomized into well-balanced groups with similar age (32 years), Injury Severity Score (25), and body mass index (27.4 kg/m2). Early metabolic support provided significantly more protein (1.43 g/kg vs. 0.35 g/kg; p < 0.0001) and more calories (12.6 kcal/kg vs. 7.5 g/kg; p = 0.0012) over the first 5 days as compared with the standard of care. Early metabolic support modified protein catabolism and synthesis as demonstrated by a larger median negative nitrogen balance (−16.3 g vs. −5.3 g; p = 0.03) and a unique metabolomic profile at day 5. The biochemical profile of patients who received EMS was defined by greater declines in circulating levels of stress hormone precursors and increased levels of amino acids. The inflammatory response following EMS resulted in a greater decrease in interleukin-1B (p = 0.02) and increase in soluble interleukin-6 receptor (p = 0.01) between baseline and day 5 as compared with the standard of care. The EMS group had a decreased length of stay (15 vs. 22 days) and decreased surgical intensive care unit length of stay (8 vs. 9 days); however, this disappeared after adjustment for Injury Severity Score in this small population.

CONCLUSIONS

Early metabolic support with amino acid is safe, modifies metabolism, and may downregulate the inflammatory state associated with significant trauma, warranting a larger trial to assess for improved outcomes.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level II.
Co-detection of the measles vaccine and wild-type virus by real-time PCR: public health laboratory protocol
Authors: Stanoeva Kamelia R. , Kohl Robert H. G. , Bodewes Rogier
Published: November 2021

In rare cases vaccination with the measles virus vaccine genotype A (MeVA) may cause a vaccine reaction with clinical signs similar to infection with wild-type measles virus (MeVwt). Rapid differentiation between MeVA and MeVwt infection is important for taking adequate public health measures. Recently, a few MeVA real-time reverse-transcription quantitative PCR methods (RT-qPCRs) were described that can distinguish between MeVA and MeVwt. However, detection of MeVA does in theory not exclude infection with MeVwt. In the present study, we established a protocol for determination of co-infections with MeVA and MeVwt. To this end, MeVA RT-qPCRs were used in combination with the routine measles virus (MeV) RT-qPCR, and the results suggested that the differences between the RT-qPCR Ct values (delta Ct, ∆Ct) could be used as criteria. Subsequently, we tested samples from vaccine-associated measles cases that were confirmed by genotyping. In addition, experimental mixtures of MeVA and MeVwt were tested in different concentrations. All tested MeVA clinical samples had ∆Ct ≤3.6. The results of experimental mixtures showed a mean ∆Ct ≤2.8 for genotype A alone and >3.2 when combined with either genotype B3 or D8. The results of a receiver operator characteristic analysis indicated that the optimum ∆Ct for use as a cut-off value was 3.5, while with ∆Ct values of 2.9 and 3.7 sensitivity and specificity were respectively 1.00. Thus, ∆Ct could be used to exclude the presence of MeVwt if MeVA is detected and ∆Ct is <2.9, while ∆Ct >3.7 were highly suggestive of co-infection and ≥2.9 ∆Ct <3.7 warranted additional confirmation, such as next-generation sequencing. This RT-qPCR-based protocol could be used for the exclusion of infection with MeVwt in cases with vaccine-associated measles reaction, crucial for the timely implementation of public health prevention and control measures.
A more compact photoacoustic imaging system to detect periodontitis
Authors: Fu Lei , Ling Chen , Jin Zhicheng , Luo Jessica , Palma-Chavez Jorge , Wu Zhuohong , Zhou Jingcheng , Zhou Jiajing , Donovan Brian , Qi Baiyan , Mishra Aditya , He Tengyu , Jokerst Jesse V.
Published: November 2021

Photoacoustic imaging has shown value in periodontal disease, but the large size of conventional photoacoustic transducers prevents imaging of more posterior teeth, i.e., molars. Here, we report a clinical “hockey stick”-style transducer repurposed for photoacoustic (PA) via an integrated fiber bundle. The shape of the hockey stick transducer facilitates imaging of the 1st pre-molars in contrast to conventional photoacoustic transducer designs. This tool was then deployed for photoacoustic imaging of periodontal disease and the periodontal pocket via a food-grade contrast agent (cuttlefish ink). We characterized the resolution and imaging range and then validated the system with a swine model and human subjects. We could image four additional teeth per quadrant with the smaller design versus a commercial photoacoustic transducer. Three raters evaluated the performance of the hockey stick transducer. The measurements between the probing and the PA methods were blinded, but the outcomes were highly correlated. We showed a bias of ∼0.3 mm for the imaging-based technique versus conventional probing. In addition, the inter-reliability was over 0.60 for three different raters of varying experience suggesting that this approach to evaluating dental health is teachable and reproducible. Finally, we demonstrated the utility in a human subject and can image teeth much more posterior in the mouth than with conventional photoacoustic transducers.
Differential age-associated brain atrophy and white matter changes among homeless and precariously housed individuals compared to the general population
Authors: Stubbs Jacob L. , Jones Andrea A. , Wolfman Daniel , Chan Ryan C. Y. , Vertinsky Alexandra T. , Heran Manraj K. , Su Wayne , Lang Donna J. , Field Thalia S. , Gicas Kristina M. , Woodward Melissa L. , Thornton Allen E. , Barr Alasdair M. , Leonova Olga , MacEwan G. William , Rauscher Alexander , Honer William G. , Panenka William J.
Published: November 2021

Importance

Homeless or precariously housed individuals live with poor health and experience premature mortality compared to the general population. With an increasing average age among this demographic, syndromes associated with neurogenerative disease are also increasing. Quantitative MRI measures may help define the roles of age and risk factors for poor brain health among these individuals.

Objective

To evaluate whether MRI measures of brain structure are differentially associated with age and selected risk factors among individuals who are homeless or precariously housed compared to a general population sample.

Design, setting, and participants

Cross sectional comparison of baseline data from 312 community-based, precariously housed participants with a publicly available dataset of 382 participants recruited from the general population.

Exposure(s)

The primary exposure was housing status (precariously housed vs general population). Risk factors in the precariously housed sample included mental illness, substance dependence, intravenous drug use, HIV, and history of traumatic brain injury.

Main outcome(s) and measure(s)

The main outcomes were MRI measures of whole-brain tissue- to-intracranial volume ratio, fractional anisotropy, and mean diffusivity. Multiple linear regression and piecewise regression were used to evaluate differences in associations between MRI measures and age between the samples, and to explore associations with risk factors in the precariously housed sample.

Results

Compared to the general population sample, older age in the precariously housed sample was associated with more whole-brain atrophy (β=-0.20, p=0.0029), lower whole-brain FA (β=-0.32, p<0.0001), and higher whole-brain MD (β=0.69, p<0.0001). Several MRI measures had non-linear associations with age, with further adverse changes after age 35-40 in the precariously housed sample. Frontal and temporal cortical thickness, corpus callosum volume, and diffusivity in the association tracts, corpus callosum, and thalamic radiations were the regions of interest most differentially affected. History of traumatic brain injury, stimulant dependence, and heroin dependence were associated with more atrophy or alterations in white matter diffusivity in the precariously housed sample.

Conclusions and relevance

Older age is associated with adverse MRI measures of brain structure among homeless and precariously housed individuals compared to the general population. Education, improvements in care provision and policy may help to reduce the health disparities experienced by these individuals.
Towards a Theory of Evolution as Multilevel Learning
Authors: Vanchurin Vitaly , Wolf Yuri I. , Katsnelson Mikhail I. , Koonin Eugene V.
Published: November 2021

We apply the theory of learning to physically renormalizable systems in an attempt to develop a theory of biological evolution, including the origin of life, as multilevel learning. We formulate seven fundamental principles of evolution that appear to be necessary and sufficient to render a universe observable and show that they entail the major features of biological evolution, including replication and natural selection. These principles also follow naturally from the theory of learning. We formulate the theory of evolution using the mathematical framework of neural networks, which provides for detailed analysis of evolutionary phenomena. To demonstrate the potential of the proposed theoretical framework, we derive a generalized version of the Central Dogma of molecular biology by analyzing the flow of information during learning (back-propagation) and predicting (forward-propagation) the environment by evolving organisms. The more complex evolutionary phenomena, such as major transitions in evolution, in particular, the origin of life, have to be analyzed in the thermodynamic limit, which is described in detail in the accompanying paper.

Significance statement

Modern evolutionary theory gives a detailed quantitative description of microevolutionary processes that occur within evolving populations of organisms, but evolutionary transitions and emergence of multiple levels of complexity remain poorly understood. Here we establish correspondence between the key features of evolution, renormalizability of physical theories and learning dynamics, to outline a theory of evolution that strives to incorporate all evolutionary processes within a unified mathematical framework of the theory of learning. Under this theory, for example, natural selection readily arises from the learning dynamics, and in sufficiently complex systems, the same learning phenomena occur on multiple levels or on different scales, similar to the case of renormalizable physical theories.
First-order visual interneurons distribute distinct contrast and luminance information across ON and OFF pathways to achieve stable behavior
Authors: Ketkar Madhura , Gür Burak , Molina-Obando Sebastian , Ioannidou Maria , Martelli Carlotta , Silies Marion
Published: November 2021

The accurate processing of contrast is the basis for all visually guided behaviors. Visual scenes with rapidly changing illumination challenge contrast computation, because adaptation is not fast enough to compensate for such changes. Yet, human perception of contrast is stable even when the visual environment is quickly changing. The fruit fly Drosophila also shows nearly luminance invariant behavior for both ON and OFF stimuli. To achieve this, first-order interneurons L1, L2 and L3 all encode contrast and luminance differently, and distribute information across both ON and OFF contrast-selective pathways. Behavioral responses to both ON and OFF stimuli rely on a luminance-based correction provided by L1 and L3, wherein L1 supports contrast computation linearly, and L3 non-linearly amplifies dim stimuli. Therefore, L1, L2 and L3 are not distinct inputs to ON and OFF pathways but the lamina serves as a separate processing layer that distributes distinct luminance and contrast information across ON and OFF pathways to support behavioral performance in varying conditions.
Severity and inpatient mortality of COVID-19 pneumonia from Beta variant infection: a clinical cohort study in Cape Town, South Africa
Authors: Boloko Linda , Lifson Aimee , Little Francesca , De Wet Timothy , Papavarnavas Nectarios , Marais Gert , Hsiao Nei-yuan , Rosslee Michael-John , Doolabh Deelan , Iranzadeh Arash , Williamson Carolyn , Dlamini Sipho , Mendelson Marc , Ntusi Ntobeko , Wilkinson Robert J. , Hussey Hannah , Davies Mary-Ann , Meintjes Graeme , Wasserman Sean
Published: November 2021

Background

The SARS-CoV-2 Beta variant, associated with immune escape and higher transmissibility, drove a more severe second COVID-19 wave in South Africa. Individual patient level characteristics and outcomes with the Beta variant are not well characterized.

Methods

We performed a retrospective cohort study comparing disease severity and inpatient mortality of COVID-19 pneumonia between the first and second wave periods at a referral hospital in Cape Town, South Africa. Beta variant infection was confirmed by genomic sequencing. Outcomes were analyzed with logistic regression and accelerated failure time models.

Results

1,182 patients were included: 571 during the first wave period and 611 from the second wave. Beta variant accounted for 97% of infections in the second wave. There was no difference in crude in-hospital mortality between wave periods (first wave 22.2%, second wave 22.1%; p = 0.9). Time to death was decreased with higher weekly hospital admissions (16%; 95% CI, 8 to 24 for every 50-patient increase), age (18%; 95% CI, 12 to 24 for every 10-year increase) and hypertension (31%; 95% CI, 12 to 46). Corticosteroid use delayed time to death by 2-fold (95% CI, 1.5 to 3.0). Admission during the second wave decreased time to death after adjustment for other predictors, but this did not reach statistical significance (24%; 95% CI, 47 to -2). There was no effect of HIV on survival.

Conclusions

There was a trend towards earlier mortality during the second COVID-19 wave driven by the Beta variant, suggesting a possible biological basis. Use of oral prednisone was strongly protective.

Key points

In Cape Town, South Africa, the second wave of COVID-19, dominated by the Beta variant, was associated with decreased time to inpatient death after adjustment for age, comorbidities, steroid use, and admission numbers. Use of oral prednisone was strongly protective.
Calorie reformulation: A systematic review and meta-analysis examining the effect of manipulating food energy density on daily energy intake and body weight
Authors: Robinson Eric , Khuttan Mercedes , McFarland-Lesser India , Patel Zina , Jones Andrew
Published: November 2021

Background

Dietary energy density is thought to be a contributor to obesity, but the extent to which different magnitudes and types of reductions to food energy density decreases daily energy intake is unclear.

Objective

To systematically review and meta-analyse experimental studies that have examined the effect that manipulating energy density of food has on total daily energy intake.

Design

A systematic review and multi-level meta-analysis of studies on human participants that used an experimental design to manipulate the energy density of foods served and measured energy intake for a minimum of one day.

Results

Thirty-one eligible studies contributed 90 effects comparing the effect of higher vs. lower energy density of served food on daily energy intake to the primary meta-analysis. Lower energy density of food was associated with a large decrease in daily energy intake (SMD = -1.002 [95% CI: -0.745 to -1.266]). Findings were consistent across studies that did vs. did not manipulate macronutrient content to vary energy density. The relation between decreasing energy density and daily energy intake tended to be strong and linear, whereby compensation for decreases to energy density of foods (i.e. by eating more at other meals) was minimal. Meta-analysis of (n=5) studies indicated that serving lower energy dense food tended to be associated with greater weight loss than serving higher energy dense food, but this difference was not significant (−0.7kg, 95% CIs: -1.34, 0.04).

Conclusions

Decreasing the energy density of food can substantially reduce daily energy intake and may therefore be an effective public health approach to reducing population level energy intake.
Chitin and cuticle proteins form the cuticular layer in spinning duct of silk-spinning arthropods
Authors: Wang Xin , Xie Xiaoqian , Xie Kang , Liu Qingsong , Li Yi , Tan Xiaoyin , Dong Haonan , Li Xinning , Dong Zhaoming , Xia Qingyou , Zhao Ping
Published: November 2021

Chitin is found in the exoskeleton and peritrophic matrix of arthropods, but recent studies have also identified chitin in the spinning duct of silk-spinning arthropods. Here, we report the presence and function of chitin and cuticle proteins ASSCP1 and ASSCP2 in the spinning duct of silkworms. We show that chitin and these proteins are co-located in the cuticular layer of the spinning duct. Ultrastructural analysis indicates that the cuticular layer has a multilayer structure by layered stacking of the chitin laminae. After knocking down ASSCP1 and ASSCP2, the fine structure of this layer was disrupted, which had negative impacts on the mechanical properties of silk. This work clarifies the function of chitin in the spinning duct of silk-spinning arthropods. Chitin and cuticle proteins are the main components of the hard and rigid cuticular layer, providing the shearing stress during silk fibrillogenesis and regulating the final mechanical properties of silk.
OMAMO: orthology-based model organism selection
Authors: Nicheperovich Alina , Altenhoff Adrian M. , Dessimoz Christophe , Majidian Sina
Published: November 2021

The conservation of pathways and genes across species has allowed scientists to use non-human model organisms to gain a deeper understanding of human biology. However, the use of traditional model systems such as mice, rats, and zebrafish is costly, time-consuming and increasingly raises ethical concerns, which highlights the need to search for less complex model organisms. Existing tools only focus on the few well-studied model systems, most of which are complex animals. To address these issues, we have developed Orthologous Matrix and Model Organisms, a software and a website that provide the user with the best simple organism for research into a biological process of interest based on orthologous relationships between the human and the species. The outputs provided by the database were supported by a systematic literature review.

Availability and implementation

https://omabrowser.org/omamo/, https://github.com/DessimozLab/omamo

Contact

christophe.dessimoz@unil.ch and sina.majidian@unil.ch
The Impact of Multivesicular Release on the Transmission of Sensory Information by Ribbon Synapses
Authors: James Ben , Piekarz Pawel , Moya-Diaz José , Lagnado Leon
Published: November 2021

The statistics of vesicle release determine how information is transferred at the synapse but the classical Poisson model of independent fusion does not hold at the first stages of vision and hearing. There, ribbon synapses encoding analogue signals can coordinate the release of two or more vesicles as a single event. The implications of such multivesicular release (MVR) for spike generation are not known. Here we investigate the hypothesis that MVR might provide advantages over Poisson synapses. We used leaky integrate-and-fire models incorporating the statistics of release measured experimentally from glutamatergic synapses of retinal bipolar cells and compared these with models assuming Poisson inputs constrained to operate at the same average rates. We find that MVR can increase the number of spikes generated per vesicle while reducing interspike intervals and latency to first spike. The combined effect was to increase the efficiency of information transfer (bits per spike) over a range of conditions mimicing retinal ganglion cells of different size. MVR was most advantageous in neurons with short time-constants and reliable synaptic inputs, when a lower degree of convergence was required to trigger spikes. In the special case of a single input driving a neuron with short time-constant, as occurs at the first synapse in hearing, MVR increased information transfer whenever spike generation required more than one vesicle. This study demonstrates how presynaptic integration of vesicles by MVR has the potential to compensate for less effective summation post-synaptically to increase the efficiency with which sensory information is transmitted.
Joint inference of exclusivity patterns and recurrent trajectories from tumor mutation trees
Authors: Luo Xiang Ge , Kuipers Jack , Beerenwinkel Niko
Published: November 2021

Cancer progression is an evolutionary process shaped by both deterministic and stochastic forces. Multi-region and single-cell sequencing of tumors enable high-resolution reconstruction of the mutational history of each tumor and highlight the extensive diversity across tumors and patients. Resolving the interactions among mutations and recovering recurrent evolutionary processes may offer greater opportunities for successful therapeutic strategies. To this end, we present a novel probabilistic framework, called TreeMHN, for the joint inference of exclusivity patterns and recurrent trajectories from a cohort of intra-tumor phylogenetic trees. Through simulations, we show that TreeMHN outperforms existing alternatives that can only focus on one aspect of the task. By analyzing datasets of blood, lung, and breast cancers, we find the most likely evolutionary trajectories and mutational patterns, consistent with and enriching our current understanding of tumorigenesis. Moreover, TreeMHN facilitates the prediction of tumor evolution and provides probabilistic measures on the next mutational events given a tumor tree, a prerequisite for evolution-guided treatment strategies.
PD-L1-expressing astrocytes act as a gate-keeper for neuroinflammation in the central nervous system of mice with traumatic brain injury
Authors: Gao Xiang , Li Wei , Syed Fahim , Yuan Fang , Li Ping , Yu Qigui
Published: November 2021

Background

Tissue damage and cellular destruction are the major events in traumatic brain injury (TBI), which trigger sterile neuroimmune and neuroinflammatory responses in the brain. While appropriate acute and transient neuroimmune and neuroinflammatory responses facilitate the repair and adaptation of injured brain tissues, prolonged and excessive neuroimmune and neuroinflammatory responses exacerbate brain damage. The mechanisms that control the intensity and duration of neuroimmune and neuroinflammatory responses in TBI largely remain elusive.

Methods

We used the controlled cortical impact (CCI) model of TBI to study the role of immune checkpoints (ICPs), key regulators of immune homeostasis, in the regulation of neuroimmune and neuroinflammatory responses in the brainin vivo.

Results

We found thatde novoexpression of PD-L1, a potent inhibitory ICP, was robustly and transiently induced in reactive astrocytes, but not in microglial cells, neurons, or oligodendrocyte progenitor cells (OPCs). These PD-L1+reactive astrocytes were highly enriched to form a dense zone around the TBI lesion. Blockade of PD-L1 signaling enlarged brain tissue cavity size, increased infiltration of inflammatory Ly-6CHighmonocytes/macrophages (M/Mϕ) but not tissue-repairing Ly-6CLow/F4/80+M/Mϕ, and worsened TBI outcomes in mice. PD-L1 gene knockout enhanced production of CCL2 that interacted with its cognate receptor CCR2 on Ly-6CHighM/Mϕto chemotactically recruit these cells into inflammatory sites. Mechanically, PD-L1 signaling in astrocytes likely exhibits dual inhibitory activities for the prevention of excessive neuroimmune and neuroinflammatory responses to TBI through(1)the PD-1/PD-L1 axis to suppress the activity of brain-infiltrating PD-1+immune cells such as PD-1+T cells, and(2)PD-L1 reverse signaling to regulate the timing and intensity of astrocyte reactions to TBI.

Conclusions

PD-L1+astrocytes act as a gatekeeper to the brain to control TBI-related neuroimmune and neuroinflammatory responses, thereby opening a novel avenue to study the role of ICP-neuroimmune axes in the pathophysiology of TBI and other neurological disorders.
miR-122 affects both the initiation and maintenance of Hepatitis C Virus infections
Authors: Panigrahi Mamata , Thibault Patricia A , Wilson Joyce A
Published: November 2021

A liver-specific microRNA, miR-122, anneals to the HCV genomic 5’ terminus and is essential for virus replication in cell culture. However, bicistronic HCV replicons and full length RNAs with specific mutations in the 5’ UTR can replicate, albeit to low levels, without miR-122. In this study, we have identified that HCV RNAs lacking the structural gene region or having EMCV IRES-regulated translation had reduced requirements for miR-122. In addition, we found that a smaller proportion of cells supported miR-122-independent replication when compared a population of cells supporting miR-122-dependent replication, while viral protein levels per positive cell were similar. Further, the proportion of cells supporting miR-122-independent replication increased with the amount of viral RNA delivered, suggesting that establishment of miR-122-independent replication in a cell is affected by amount of viral RNA delivered. HCV RNAs replicating independent of miR-122 were not affected by supplementation with miR-122, suggesting that miR-122 is not essential for maintenance of a miR-122-independent HCV infection. However, miR-122 supplementation had a small positive impact on miR-122-dependent replication suggesting a minor role in enhancing ongoing virus RNA accumulation. We suggest that miR-122 functions primarily to initiate an HCV infection but has a minor influence on its maintenance, and we present a model in which miR-122 is required for replication complex formation at the beginning of an infection, and also supports new replication complex formation during ongoing infection and after infected cell division.

IMPORTANCE

The mechanism by which miR-122 promotes the HCV life cycle is not well understood, and a role in directly promoting genome amplification is still debated. In this study, we have shown that miR-122 increases the rate of viral RNA accumulation and promotes the establishment of an HCV infection in a greater number of cells than in the absence of miR-122. However, we also confirm a minor role in promoting ongoing virus replication and propose a role in the initiation of new replication complexes throughout a virus infection. This study has implications for the use of anti-miR-122 as potential HCV therapy.
Sexual reproduction contributes to the evolution of resistance breaking isolates of the spinach pathogen Peronospora effusa
Authors: Skiadas Petros , Klein Joël , Monnens Thomas Quiroz , Elberse Joyce , de Jonge Ronnie , Van den Ackerveken Guido , Seidl Michael F.
Published: November 2021

Peronospora effusa causes downy mildew, the economically most important disease of cultivated spinach worldwide. To date, 19 P. effusa races have been denominated based on their capacity to break spinach resistances, but their genetic diversity and the evolutionary processes that contribute to race emergence are unknown. Here, we performed the first systematic analysis of P. effusa races showing that those emerge by both asexual and sexual reproduction. Specifically, we studied the diversity of 26 P. effusa isolates from 16 denominated races based on mitochondrial and nuclear comparative genomics. Mitochondrial genomes based on long-read sequencing coupled with diversity assessment based on short-read sequencing uncovered two mitochondrial haplogroups, each with distinct genome organization. Nuclear genome-wide comparisons of the 26 isolates revealed that ten isolates from six races could clearly be divided into three asexually evolving groups, in concordance with their mitochondrial phylogeny. The remaining isolates showed signals of reticulated evolution and discordance between nuclear and mitochondrial phylogenies, suggesting that these evolved through sexual reproduction. Increased understanding of this pathogen’s reproductive modes will provide the framework for future studies into the molecular mechanisms underlying race emergence and into the P. effusa-spinach interaction, thus assisting in sustainable production of spinach through knowledge-driven resistance breeding.

Significance statement

Many microbial plant pathogens depend on the successful colonization of their hosts to complete their life cycle, thereby damaging food crops worldwide. The most effective way of disease control is to deploy genetic disease resistances. However, the extensive use of resistant crop varieties exerts strong selective pressure on microbial plant pathogens to adapt in order to escape resistance. Through yet unknown mechanisms, the spinach pathogen Peronospora effusa can rapidly break the resistance of newly introduced varieties, often within a single growing season. Thus, there is an urgent need to better understand the mechanisms driving adaptation in P. effusa. This information will lead the way to knowledge-driven resistance breeding. Here, we capture for the first time the genetic variation of 26 P. effusa, 16 of which can break a different combination of host resistances. We demonstrate that P. effusa isolates evolve by both asexual and sexual reproduction, and thereby provide the framework to study the molecular mechanisms of the interactions between P. effusa and spinach.
CDK5 mediated phosphorylation of cytosolic phospholipase A2 regulates its activity and neuroinflammation in Parkinson’s Disease
Authors: Paul Sangita , Fatihi Saman , Sharma Srishti , Kutum Rintu , Fields Raymond , Pant Harish C , Thukral Lipi , Binukumar BK
Published: November 2021

Hyperactivation of cyclin-dependent kinase 5 (CDK5) by p25, contributes to neuroinflammation causing neurodegeneration in Parkinson’s Disease (PD) and Alzheimer diseases (AD). However, the mechanism by which CDK5 induces neuroinflammation in the PD brain is largely unexplored. Here, we show that CDK5 phosphorylates cytosolic phospholipase A2 (cPLA2) at Thr-268 and Ser-505 sites lead to its activation and generation of eicosanoid products. Mutational studies using site-directed mutagenesis and molecular simulations show that the architecture of the protein changes upon each single-point mutation. Interestingly, double-mutations also led to severe decline in the activity of cPLA2 and disruption of its translocation to the plasma membrane. Further, the brain lysates of transgenic PD mouse models show hyperactivation of CDK5 resulting in enhanced phosphorylation of Thr-268 and Ser-505 of cPLA2 and its heightened activity confirming the findings observed in the cell culture model of PD. These phosphorylation sites of cPLA2 and CDK5 could be explored as the future therapeutic targets against neuroinflammation in PD. Further, conjoint transcriptomic analysis of the publicly available human PD datasets strengthens the hypothesis that genes of the arachidonic acid, prostaglandin synthesis and inflammatory pathways are significantly upregulated in case of the PD patients as compared to that of healthy controls.
Multiplex Embedding of Biological Networks Using Topological Similarity of Different Layers
Authors: Coşkun Mustafa , Koyutürk Mehmet
Published: November 2021

Network embedding techniques, which provide low dimensional representations of the nodes in a network, have been commonly applied to many machine learning problems in computational biology. In most of these applications, multiple networks (e.g., different types of interactions/associations or semantically identical networks that come from different sources) are available. Multiplex network embedding aims to derive strength from these data sources by integrating multiple networks with a common set of nodes. Existing approaches to this problem treat all layers of the multiplex network equally while performing integration, ignoring the differences in the topology and sparsity patterns of different networks. Here, we formulate an optimization problem that accounts for inner-network smoothness, intra-network smoothness, and topological similarity of networks to compute diffusion states for each network. To quantify the topological similarity of pairs of networks, we use Gromov-Wasserteins discrepancy. Finally, we integrate the resulting diffusion states and apply dimensionality reduction (singular value decomposition after log-transformation) to compute node embeddings. Our experimental results in the context of drug repositioning and drug-target prediction show that the embeddings computed by the resulting algorithm, Hattusha, consistently improve predictive accuracy over algorithms that do not take into account the topological similarity of different networks.