bluuebunny/crossref_metadata_2025 huggingface dataset:
Rehabilitation Response in Pandemics
Authors: Amatya Bhasker , Khan Fary
Published: May 2020

The World Health Organization declared a pandemic due to the serious health risk posed by coronavirus disease (COVID-19). The number of infected cases is on the rise globally with escalating human, economic, and societal costs. Survivors of COVID-19 may experience a range of clinical, functional, and psychological impairments, resulting in disabilities. Many are amenable to rehabilitation intervention. The current focus of COVID-19 management is on public health measures and acute management. As patients transfer to subacute care or discharged to the community, rehabilitation services need to have a number of organizational and operational models in place to provide safe and effective care for patients and health professionals.

There is need for global action by professional organizations in developing a structured rehabilitation approach for international response to disasters, including pandemics. This report proposes development of a “Rehabilitation Response Plan” to enable the International Society of Physical and Rehabilitation Medicine, to provide crucial leadership and governance role in liaison and coordination with the World Health Organization (and other stakeholders), to provide rehabilitation input during current and future pandemics. The key considerations include following categories: governance, coordination, communication, evaluation, and care continuum. These will strengthen rehabilitation, assist in the effective delivery of services, and provide advocacy and an international coordinated perspective.
Rhinoplasty Refinements: Addressing the Deviated, Overprojected Nose
Authors: Rohrich Rod. J. , Shanmugakrishnan R. Raja , Mohan Raja
Published: May 2020

Deprojection of an overprojected nose and correction of an infralobular deformity are very challenging for rhinoplasty surgeons because a systematic approach is needed to correct these problems. A deviated nose with a dorsal hump is a common deformity that is best treated using septal reconstruction and the component dorsal hump reduction technique using an open rhinoplasty approach. This article and its videos show how to correct a deviated nose with overprojection and a dorsal hump deformity.
Laparoscopically Assisted DIEP Flap Harvest Minimizes Fascial Incision in Autologous Breast Reconstruction
Authors: Shakir Sameer , Spencer Amy B. , Kozak Geoffrey M. , Nathan Shelby L. , Soriano Ian S. , Kanchwala Suhail K.
Published: May 2020

Background:

Total extraperitoneal laparoscopically assisted harvest of the deep inferior epigastric vessels permits a decrease in myofascial dissection in deep inferior epigastric artery perforator flap breast reconstruction. The authors present a reliable technique that further decreases donor-site morbidity in autologous breast reconstruction.

Methods:

The authors conducted a retrospective cohort study of female subjects presenting to the senior surgeon (S.K.K.) from March of 2018 to March of 2019 for autologous breast reconstruction after a newly diagnosed breast cancer. The operative technique is summarized as follows: a supraumbilical camera port is placed at the medial edge of the rectus muscle to enter the retrorectus space; the extraperitoneal plane is developed using a balloon dissector and insufflation; two ports are placed through the linea alba below the umbilicus to introduce dissection instruments; the deep inferior epigastric vessels are dissected from the underside of the rectus muscle; muscle branches and the superior epigastric are ligated using a Ligasure; and the deep inferior epigastric pedicle is ligated and the vessels are delivered through a minimal fascial incision. The flap(s) is transferred to the chest for completion of the reconstruction.

Results:

Thirty-three subjects totaling 57 flaps were included. All flaps were single-perforator deep inferior epigastric artery perforator flaps. Mean fascial incision length was 2.0 cm. Sixty percent of subjects recovered without narcotics. Mean length of stay was 2.5 days. Flap salvage occurred in one subject after venous congestion. Two pedicle transections occurred during harvest that required perforator-to-pedicle anastomosis.

Conclusion:

Total extraperitoneal laparoscopically assisted harvest of the deep inferior epigastric pedicle is a reliable method that decreases the donor-site morbidity of autologous breast reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
In-Depth Look at the Anatomical Relationship of the Lesser Occipital Nerve, Great Auricular Nerve, and Spinal Accessory Nerve and Their Implication in Safety of Operations in the Posterior Triangle of the Neck
Authors: Amirlak Bardia , Lu Karen B. , Erickson Cameron R. , Sanniec Kyle , Totonchi Ali , Peled Ziv M. , Cheng Jonathan C.
Published: May 2020

Background:

Migraine surgery is an increasingly popular treatment option for migraine patients. The lesser occipital nerve is a common trigger point for headache abnormalities, but there is a paucity of research regarding the lesser occipital nerve and its intimate association with the spinal accessory nerve.

Methods:

Six cadaver necks were dissected. The lesser occipital, great auricular, and spinal accessory nerves were identified and systematically measured and recorded. These landmarks included the longitudinal axis (vertical line drawn in the posterior), the horizontal axis (defined as a line between the most anterosuperior points of the external auditory canals) and the earlobe. Mean distances and standard deviations were calculated to delineate the relationship between the spinal accessory, lesser occipital, and great auricular nerves.

Results:

The point of emergence of the spinal accessory nerve was determined to be 7.17 ± 1.15 cm lateral to the y axis and 7.77 ± 1.10 caudal to the x axis. The lesser occipital nerve emerges 7.5 ± 1.31 cm lateral to the y axis and 8.47 ± 1.11 cm caudal to the x axis. The great auricular nerve emerges 8.33 ± 1.31 cm lateral to the y axis and 9.4 ±1.07 cm caudal to the x axis. The decussation of the spinal accessory and the lesser occipital nerves was found to be 7.70 ± 1.16 cm caudal to the x axis and 7.17 ± 1.15 lateral to the y axis.

Conclusion:

Understanding the close relationship between the lesser occipital nerve and spinal accessory nerve in the posterior, lateral neck area is crucial for a safer approach to occipital migraine headaches, occipital neuralgia, and new daily persistent headaches and other reconstructive or cosmetic operations.
FDG Uptake in Brown Adipose Tissue Activated by a β3-Adrenergic Receptor Agonist Prescribed for Overactive Bladder
Authors: Okuyama Chio , Kikuchi Ryutaro , Ikeuchi Takashi
Published: May 2020

Brown adipose tissue (BAT), which produces energy and is known to play a role as a hibernating gland, is sometimes visualized on 18F-FDG PET in children or in slender young adults in a cold environment. Because BAT is activated by catecholamines, FDG uptake in BAT is also observed in patients with pheochromocytoma or paraganglioma. We present the case of an elderly woman with remarkable FDG uptake in BAT. Activation of BAT by a β3-adrenergic receptor agonist (mirabegron) prescribed for overactive bladder was suspected as the cause of the marked visualization of BAT in this patient.
Osteitis Fibrosa Cystica Caused by Hyperparathyroidism Shown on 18F-NaF PET/CT
Authors: Deng Yan , Shen Xing , Lei Lei , Zhang Wei
Published: May 2020

18F-NaF PET/CT in hyperparathyroidism and osteitis fibrosa cystica is rarely reported. We report the case of a 16-year-old boy who underwent NaF PET/CT for the evaluation of bilateral bone destruction, which was incidentally noted on an abdominal x-ray. The PET/CT images identified multiple bony abnormalities in the skull, pelvis, and limbs. In addition, a hypodense nodule was found posterior to the inferior pole of the right lobe of thyroid gland. Subsequent 99mTc-sestamibi imaging showed abnormal uptake in the neck nodule, which was confirmed as parathyroid adenoma by the pathology.
Intraoperative Detection of Hyperplastic Parathyroid Gland With Positron Emitter 18F-Fluorocholine and Handheld Probe
Authors: Golubić Anja Tea , Poljak Frano , Bumber Boris , Huić Dražen
Published: May 2020

We present the first intraoperative detection of a hyperplastic parathyroid gland with a positron emitter 18F-fluorocholine and handheld probe, with the estimation of the absorbed dose to the surgeon and surgical staff. Intraoperative positron emitter detection enabled the resection of a small parathyroid gland, resulting in normal postoperative values of PTH and serum calcium in a 69-year-old woman. Calculated whole-body dose to the surgical staff and surgeons’ fingers is well below the annual limits for exposed workers and the general public. Intraoperative 18F-FCH detection with handheld probe is a safe and feasible method for localizing small parathyroid glands.
Three-dimensional Ultrashort Echotime Magnetic Resonance Imaging for Combined Morphologic and Ventilation Imaging in Pediatric Patients With Pulmonary Disease
Authors: Veldhoen Simon , Heidenreich Julius F. , Metz Corona , Petritsch Bernhard , Benkert Thomas , Hebestreit Helge U. , Bley Thorsten A. , Köstler Herbert , Weng Andreas M.
Published: May 2020

Purpose:

Ultrashort echotime (UTE) sequences aim to improve the signal yield in pulmonary magnetic resonance imaging (MRI). We demonstrate the initial results of spiral 3-dimensional (3D) UTE-MRI for combined morphologic and functional imaging in pediatric patients.

Methods:

Seven pediatric patients with pulmonary abnormalities were included in this observational, prospective, single-center study, with the patients having the following conditions: cystic fibrosis (CF) with middle lobe atelectasis, CF with allergic bronchopulmonary aspergillosis, primary ciliary dyskinesia, air trapping, congenital lobar overinflation, congenital pulmonary airway malformation, and pulmonary hamartoma.

Patients were scanned during breath-hold in 5 breathing states on a 3-Tesla system using a prototypical 3D stack-of-spirals UTE sequence. Ventilation maps and signal intensity maps were calculated. Morphologic images, ventilation-weighted maps, and signal intensity maps of the lungs of each patient were assessed intraindividually and compared with reference examinations.

Results:

With a scan time of ∼15 seconds per breathing state, 3D UTE-MRI allowed for sufficient imaging of both “plus” pathologies (atelectasis, inflammatory consolidation, and pulmonary hamartoma) and “minus” pathologies (congenital lobar overinflation, congenital pulmonary airway malformation, and air trapping). Color-coded maps of normalized signal intensity and ventilation increased diagnostic confidence, particularly with regard to “minus” pathologies. UTE-MRI detected new atelectasis in an asymptomatic CF patient, allowing for rapid and successful therapy initiation, and it was able to reproduce atelectasis and hamartoma known from multidetector computed tomography and to monitor a patient with allergic bronchopulmonary aspergillosis.

Conclusion:

3D UTE-MRI using a stack-of-spirals trajectory enables combined morphologic and functional imaging of the lungs within ~115 second acquisition time and might be suitable for monitoring a wide spectrum of pulmonary diseases.
Peer-Led Education Expedites Deprescribing Proton Pump Inhibitors for Appropriate Veterans
Authors: Bowman Mary H.
Published: May 2020

Costly proton pump inhibitors have been widely prescribed since the 1990s for prevention and treatment of ulcers and gastroesophageal reflux disease. Evidence published since 2012 demonstrates risks associated with taking proton pump inhibitors for longer than 8 weeks. Primary care providers mostly deprescribe proton pump inhibitors for persons not meeting criteria for long-term use. Many patients resist discontinuation.

A 3-month evidence-based practice education project was conducted by a nurse practitioner to improve primary care provider peer deprescribing successes with appropriate patients in an outpatient California-based veteran primary care clinic. Fifteen primary care providers were pretested about usual care practices between 2 comparable clinics. Five primary care providers at the smaller clinic location were educated about long-term proton pump inhibitor use risks and introduced to 3 evidence-based practice guidelines using tapering techniques with follow-up care.

A Canadian 2017 evidence-based practice proton pump inhibitor deprescribing guideline was proposed for translation into practice. Primary care providers voted to pilot this guideline, dependent upon nursing support. Primary care providers denied frustration with usual care practices, even as all were willing to try an evidence-based practice change between pre- and post-test surveys. Support for peer-led evidence-based practice on-site coaching increased from 87% to 100%. Tapering behavior increased from 67% to 100%, expediting improved long-term medication cessation.
Prehospital Point of Care Testing for the Early Detection of Shock and Prediction of Lifesaving Interventions
Authors: Galvagno Samuel M. , Sikorski Robert A. , Floccare Douglas J. , Rock Peter , Mazzeffi Michael A. , DuBose Joseph J. , Scalea Thomas M. , Miller Catriona , Richards Justin E. , O’Connor James V. , Mackenzie Colin F. , Hu Peter
Published: May 2020

Introduction:

Early diagnosis and treatment are essential for enhancing outcomes for the traumatically injured. In this prospective prehospital observational study, we hypothesized that a variety of laboratory results measured in the prehospital environment would predict both the presence of early shock and the need for lifesaving interventions (LSIs) for adult patients with traumatic injuries.

Methods:

Adult trauma patients flown by a helicopter emergency medical service were prospectively enrolled. Using an i-STAT portable analyzer, data from 16 laboratory tests were collected. Vital signs data were also collected. Outcomes of interest included detection of shock, mortality, and requirement for LSIs. Logistic regression, including a Bayesian analysis, was performed.

Results:

Among 300 patients screened for enrollment, 261 had complete laboratory data for analysis. The majority of patients were male (75%) with blunt trauma (91.2%). The median injury severity score was 29 (IQR, 25–75) and overall mortality was 4.6%. A total of 170 LSIs were performed. The median lactate for patients who required an LSI was 4.1 (IQR, 3–5.4). The odds of requiring an LSI within the first hour of admission to the trauma center was highly associated with increases in lactate and glucose. A lactate level > 4 mmol/L was statistically associated with greater sensitivity and specificity for predicting the need for a LSI compared with shock index.

Conclusions:

In this prospective observational trial, lactate outperformed static vital signs, including shock index, for detecting shock and predicting the need for LSIs. A lactate level > 4 mmol/L was found to be highly associated with the need for LSIs.
Management Considerations for the Surgical Treatment of Colorectal Cancer During the Global Covid-19 Pandemic
Authors: O’Leary Michael P. , Choong Kevin C. , Thornblade Lucas W. , Fakih Marwan G. , Fong Yuman , Kaiser Andreas M.
Published: May 2020

Objective:

The COVID-19 pandemic requires to conscientiously weigh “timely surgical intervention” for colorectal cancer against efforts to conserve hospital resources and protect patients and health care providers.

Summary Background Data:

Professional societies provided ad-hoc guidance at the outset of the COVID-19 pandemic on deferral of surgical and perioperative interventions, but these lack specific parameters to determine the optimal timing of surgery.

Methods:

Using the GRADE system, published evidence was analyzed to generate weighted statements for stage, site, acuity of presentation, and hospital setting to specify when surgery should be pursued, the time and duration of oncologically acceptable delays, and when to utilize nonsurgical modalities to bridge the waiting period.

Results:

Colorectal cancer surgeries—prioritized as emergency, urgent with imminent emergency or oncologically urgent, or elective—were matched against the phases of the pandemic. Surgery in COVID-19-positive patients must be avoided. Emergent and imminent emergent cases should mostly proceed unless resources are exhausted. Standard practices allow for postponement of elective cases and deferral to nonsurgical modalities of stage II/III rectal and metastatic colorectal cancer. Oncologically urgent cases may be delayed for 6(–12) weeks without jeopardizing oncological outcomes. Outside established principles, administration of nonsurgical modalities is not justified and increases the vulnerability of patients.

Conclusions:

The COVID-19 pandemic has stressed already limited health care resources and forced rationing, triage, and prioritization of care in general, specifically of surgical interventions. Established guidelines allow for modifications of optimal timing and type of surgery for colorectal cancer during an unrelated pandemic.
Association of ovarian hormones with mapping concept of self and others in the brain’s default mode network.
Authors: Wang Jia-Xi , Zhuang Jin-Ying , Fu Lulu , Lei Qin , Zhang Weidong
Published: May 2020

The brain’s default mode network (DMN) has become closely associated with self-referential mental activity, particularly in the resting-state. Prior reports point that the sex hormones are potent modulators of brain plasticity and functional connectivity. However, it is uncertain whether changes in ovarian hormones, as occur during the monthly menstrual cycle, substantially affects the functional connectivity of DMN. Here, we employed a Self-Awareness Scale (SAS) and the resting-state functional MRI in the late follicular phase and the mid-luteal phase to investigate the effect of the estradiol (E2) and progesterone on the SAS and DMN. On the behavioral level, increased progesterone facilitated women’s other-focused attention. The regions of interest-based resting-state functional connectivity analyses continued to demonstrate a negative correlation of the relative progesterone and the medial prefrontal cortex-inferior temporal gyrus (mPFC-ITG) functional connectivity, and a facilitated effect of relative E2 on the mPFC-inferior parietal lobule functional connectivity in the DMN. Furthermore, as a core hub of the ‘theory of mind’, the functional connectivity between the ITG and thalamus was found negatively correlated with the relative E2. Meanwhile, the mid-luteal phase, which had significantly lower relative E2 levels, was indicated had stronger ITG-thalamus functional connectivity during the resting state. These results demonstrated an opposite effect of E2 and progesterone on the DMN and the other-focused preference in the mid-luteal phase, extended previous evidence of the potentially adaptive psychological effects of ovarian hormones on mapping self and others in the brain networks.
Programming and simulating chemical reaction networks on a surface
Authors: Clamons Samuel , Qian Lulu , Winfree Erik
Published: May 2020

Models of well-mixed chemical reaction networks (CRNs) have provided a solid foundation for the study of programmable molecular systems, but the importance of spatial organization in such systems has increasingly been recognized. In this paper, we explore an alternative chemical computing model introduced by Qian & Winfree in 2014, the surface CRN, which uses molecules attached to a surface such that each molecule only interacts with its immediate neighbours. Expanding on the constructions in that work, we first demonstrate that surface CRNs can emulate asynchronous and synchronous deterministic cellular automata and implement continuously active Boolean logic circuits. We introduce three new techniques for enforcing synchronization within local regions, each with a different trade-off in spatial and chemical complexity. We also demonstrate that surface CRNs can manufacture complex spatial patterns from simple initial conditions and implement interesting swarm robotic behaviours using simple local rules. Throughout all example constructions of surface CRNs, we highlight the trade-off between the ability to precisely place molecules and the ability to precisely control molecular interactions. Finally, we provide a Python simulator for surface CRNs with an easy-to-use web interface, so that readers may follow along with our examples or create their own surface CRN designs.
What he may seem to the world: Isaac Newton's autograph book epigrams
Authors: Gömöri George , Snobelen Stephen D.
Published: May 2020

This paper identifies, describes and analyses Isaac Newton's known inscriptions in
alba amicorum
(autograph books). It begins with an introduction to the early modern autograph book and its social utility for travelling students. Each Newton inscription is contextualized with brief biographies of the individual album owners. The potential reasons for Newton's use of his chosen epigrams are considered, as are possible reflexive dynamics between him and the album owners that may have helped to inform these choices. An allied consideration is the degree to which Newton's epigrams relate to scholarly projects with which he was engaged when he penned them. A special feature is the identification of the owner of an album from which a Newton inscription was stolen more than half a century ago. This study offers a glimpse of Newton's intellectual reputation across several decades, both on the Continent and in his native England. More broadly, this paper makes contributions to our understanding of Newton's personal life and the strategic use of
alba amicorum
in the late seventeenth and early eighteenth centuries within the Republic of Letters.
Confidence in confidence distributions!
Authors: Cunen Céline , Hjort Nils Lid , Schweder Tore
Published: May 2020

The recent article ‘Satellite conjunction analysis and the false confidence theorem’ (Balch
et al
. 2019, Satellite conjunction analysis and the false confidence theorem.
Proc. R. Soc. A
475
, 20180565) points to certain difficulties with Bayesian analysis when used for models for satellite conjuntion and ensuing operative decisions. Here, we supplement these previous analyses and findings with further insights, uncovering what we perceive of as being the crucial points, explained in a prototype set-up where exact analysis is attainable. We also show that a different and frequentist method, involving confidence distributions, is free of the false confidence syndrome.
Universal metabolic constraints shape the evolutionary ecology of diving in animals
Authors: Verberk Wilco C. E. P. , Calosi Piero , Brischoux François , Spicer John I. , Garland Theodore , Bilton David T.
Published: May 2020

Diving as a lifestyle has evolved on multiple occasions when air-breathing terrestrial animals invaded the aquatic realm, and diving performance shapes the ecology and behaviour of all air-breathing aquatic taxa, from small insects to great whales. Using the largest dataset yet assembled, we show that maximum dive duration increases predictably with body mass in both ectotherms and endotherms. Compared to endotherms, ectotherms can remain submerged for longer, but the mass scaling relationship for dive duration is much steeper in endotherms than in ectotherms. These differences in diving allometry can be fully explained by inherent differences between the two groups in their metabolic rate and how metabolism scales with body mass and temperature. Therefore, we suggest that similar constraints on oxygen storage and usage have shaped the evolutionary ecology of diving in all air-breathing animals, irrespective of their evolutionary history and metabolic mode. The steeper scaling relationship between body mass and dive duration in endotherms not only helps explain why the largest extant vertebrate divers are endothermic rather than ectothermic, but also fits well with the emerging consensus that large extinct tetrapod divers (e.g. plesiosaurs, ichthyosaurs and mosasaurs) were endothermic.
Smartphone applications in the prevention of Type 2 Diabetes Mellitus: a protocol for a systematic review
Authors: Jahan Esrat , Almansour Rawan , Ijaz Kiran , Ronto Rimante , Laranjo Liliana
Published: May 2020

Diabetes mellitus is a leading cause of concern among non-communicable diseases worldwide, with its prevalence increasing every day. Studies have shown that it is possible to prevent type 2 diabetes in high risk people if they adopt a healthy lifestyle, such as exercising regularly, eating nutritious food and maintaining an ideal weight. Mobile apps may aid these people in maintaining a healthy lifestyle. Till date, no systematic review has evaluated the use of mobile health applications for the prevention of type 2 diabetes. In this systematic review protocol we will lay out the methods we will use to synthesise the evidence about mobile health applications for the prevention of type 2 diabetes, focusing particularly on their impact on different process and outcome measures, as well as on patient perspectives. Database searches will be done in PubMed, Embase, CINAHL and PsychInfo. Screening of the articles will be conducted by two independent researchers. The Cochrane risk of bias tool will be used for quality assessment. A narrative synthesis of the included articles will be done and the results summarised. The findings of this review will provide evidence on the impact of mobile applications in preventing Type 2 diabetes mellitus.
Estimation of Case Fatality Rate during an Epidemic: an Example from COVID-19 Pandemic
Authors: Yunesian Masud , Fotouhi Akbar , Aghaei Mina
Published: May 2020

The case fatality rate (CFR) is an important index in epidemics and policymakers need to be aware of this statistic for making sound decisions. However, there are some uncertainties in the calculation of the fatality rate and the true case fatality rate can be calculated after an epidemic subsides, we calculated the fatality rate for 20 countries which had the highest number of confirmed cases with three scenarios. In this study, we provided detailed information to discuss the studies that calculate the case fatality rate during the COVID-19 pandemic and highlight the estimation bias in these studies
Oscillatory dynamics in infectivity and death rates of COVID-19
Authors: Pavlíček Tomáš , Rehak Pavel , Král Petr
Published: May 2020

The analysis of systematically collected data for COVID-19 infectivity and death rates has revealed in many countries around the world a typical oscillatory pattern with a 7-days (circaseptan) period. Additionally, in some countries the 3.5-days (hemicircaseptan) and 14-days periodicities have been also observed. Interestingly, the 7-days infectivity and death rates oscillations are almost in phase, showing local maxima on Thursdays/Fridays and local minima on Sundays/Mondays. These observations are in stark contrast with a known pattern, correlating the death rate with the reduced medical staff in hospitals on the weekends. One possible hypothesis addressing these observations is that they reflect a gradually increasing stress with the progressing week, which can trigger the maximal death rates observed on Thursdays/Fridays. Moreover, assuming the weekends provide the likely time for new infections, the maximum number of new cases might fall again on Thursdays/Fridays. These observations deserve further study to provide better understanding of the COVID-19 dynamics.
Calories delivered by nonhuman primate foraging enrichment: Data and methods to inform decisions concerning the dietary consequences of enrichment
Authors: Pierre Peter J. , Torres Nicolette A. , Rosga Michele , Sullivan Jennifer
Published: May 2020

Foraging opportunities are a key component of enrichment in captive nonhuman primates providing manipulative opportunities in which animals can engage in species-typical behaviors. Recent studies suggest captive NHP populations have increased body weight over time leading to negative health outcomes. Increasing food foraging opportunities provides added calories that can be estimated but often are not directly measured. We assessed 10 commonly used foraging puzzles for the amount of foraging material they held; evaluated the range of caloric content delivered; and determine the labor and usage cost of each. Five preparation areas were sampled. The amount of foraging material contained in each prepared puzzle was calculated by subtracting the average empty puzzle weight from the loaded puzzle weight. A detailed description of food content was used to illustrate caloric content. Larger prepared puzzles held more food (M=104.9 g) as compared to small volumes puzzles (M=59.8 g). Analysis of the weight of food applied and caloric content suggest larger puzzles do have the potential to provide increased caloric load; however, the added food from large foraging puzzles constitutes only 5%-10% of the daily k/cal dietary requirement. The study illustrates the importance of considering puzzle characteristics when selecting foraging toys and discusses the considerations of cost of puzzle deployment, maintenance and interactive benefit. The broad significance of our assessment suggests that calories from foraging opportunities are not excessive and can be managed by adopting standard serving sizes and scheduling intermitted presentation of non-nutritive enrichment options.
Increasing the gradient of energetic cost does not initiate adaptation in human walking
Authors: Simha Surabhi N. , Wong Jeremy D. , Selinger Jessica C. , Abram Sabrina J. , Donelan J. Maxwell
Published: May 2020

When in a new situation, the nervous system may benefit from adapting its control policy. In determining whether or not to initiate this adaptation, the nervous system may rely on some features of the new situation. Here we tested whether one such feature is salient cost savings. We changed cost saliency by manipulating the gradient of participants’ energetic cost landscape during walking. We hypothesized that steeper gradients would cause participants to spontaneously adapt their step frequency to lower costs. To manipulate the gradient, a mechatronic system applied controlled fore-aft forces to the waist of participants as a function of their step frequency as they walked on a treadmill. These forces increased the energetic cost of walking at high step frequencies and reduced it at low step frequencies. We successfully created three cost landscapes of increasing gradients, where the natural variability in participants’ step frequency provided cost changes of 3.6% (shallow), 7.2% (intermediate) and 10.2% (steep). Participants did not spontaneously initiate adaptation in response to any of the gradients. Using metronome-guided walking— a previously established protocol for eliciting initiation of adaptation—participants next experienced a step frequency with a lower cost. Participants then adapted by −1.41±0.81 (p=0.007) normalized units away from their originally preferred step frequency obtaining cost savings of 4.80±3.12%. That participants would adapt under some conditions, but not in response to steeper cost gradients, suggests that the nervous system does not solely rely on the gradient of energetic cost to initiate adaptation in novel situations.
Influence of Supraphysiologic Biomaterial Stiffness on Ventricular Mechanics and Myocardial Infarct Reinforcement
Authors: Ghanta Ravi K. , Zhao Yunge , Pugazenthi Aarthi , Wall Mathew J. , Russell Lauren N. , Lampe Kyle J.
Published: May 2020

Injectable intramyocardial biomaterials have promise to limit adverse ventricular remodeling through mechanical and biologic mechanisms. While some success has been observed by injecting materials to regenerate new tissue, optimal biomaterial stiffness to thicken and stiffen infarcted myocardium to limit adverse remodeling has not been determined. In this work, we present an in-vivo study of the impact of biomaterial stiffness over a wide range of stiffness moduli on ventricular mechanics. We utilized injectable methacrylated polyethylene glycol (PEG) hydrogels fabricated at 3 different mechanical moduli: 5 kPa (low), 25 kPa (medium/myocardium), and 250 kPa (high/supraphysiologic). We demonstrate that the supraphysiological high stiffness favorably alters post-infarct ventricular mechanics and prevents negative tissue remodeling. Lower stiffness materials do not alter mechanics and thus to be effective, must instead target biological reparative mechanisms. These results may influence rationale design criteria for biomaterials developed for infarct reinforcement therapy.
Gwas and Genomic Selection For Increased Anthocyanin Content in Purple Corn
Authors: Chatham Laura A. , Juvik John A.
Published: May 2020

Purple corn offers an attractive source of economical natural anthocyanin-based colorant for use in foods and beverages. Yet to maximize the scalability and meet growing demands, both anthocyanin concentrations and agronomic performance must improve in purple corn varieties. We studied flux through the flavonoid biosynthesis pathway using GWAS data derived from a diverse purple corn landrace with anthocyanin-rich pericarp, Apache Red. Trends between flavonoid endpoints suggest that regulators of total flux into the pathway and regulators of partitioning within the pathway may both represent targets for maximizing anthocyanin content. A peak at the end of chromosome 1 nearAat1 (Anthocyanin acyltransferase1) was highly significant in all approaches taken to map anthocyanin flux, suggesting the structural modification of malonylation is required for maximal anthocyanin production. We also identified several candidate MATEs and H+ATPases that could assist in the preferential transport of acylated anthocyanins into the vacuole. These and other candidates identified here suggest there is still much to learn about the regulation of anthocyanin biosynthesis in the pericarp of purple corn. The efficacy of genomic predictions in the population was also studied, yielding an accuracy of 0.71 with cross validation for total anthocyanin content with no improvement found when known anthocyanin regulators were added to the model. These data suggest that genomic selection could be employed effectively in a purple corn breeding program, and especially for a landrace improvement program.
BCG vaccination and socioeconomic variables vs Covid-19 global features: clearing up a controversial issue
Authors: Ventura Luigi , Vitali Matteo , Spica Vincenzo Romano
Published: May 2020

Background

The Covid-19 pandemic is characterized by extreme variability in the outcome distribution and mortality rates across different countries. Some recent studies suggested an inverse correlation with BCG vaccination at population level, while others denied this hypothesis. In order to address this controversial issue, we performed a strict epidemiological study collecting data available on a global scale, considering additional variables such as cultural-political factors and adherence to other vaccination coverages.

Methods

Data on 121 countries, accounting for about 99% of Covid-19 cases and deaths globally, were from John’s Hopkins Coronavirus Resource Center, World Bank, International Monetary Fund, United Nations, Human Freedom Report, and BCG Atlas. Statistical models used were Ordinary Least Squares, Tobit and Fractional Probit, implemented on Stata/MP16 software.

Results

Based on our results, countries where BCG vaccination is or has been mandated in the last decades have seen a drastic reduction in Covid-19 diffusion (−80% on average) and mortality (−50% on average), even controlling for relative wealth of countries and their governmental health expenditure. A significant contribution to this reduction (respectively −50% and −13% on average) was also associated to the outbreak onset during summer, suggesting a possible influence of seasonality. Other variables turned out to be associated, though to a lesser extent.

Conclusions

Relying on a very large dataset and a wide array of control variables, our study confirms a strong and robust association between Covid-19 diffusion and mortality with BCG vaccination and a set socio-economic factors, opening new perspectives for clinical speculations and public health policies.
Phase-dependent closed-loop modulation of neural oscillations in vivo
Authors: McNamara Colin G. , Rothwell Max , Sharott Andrew
Published: May 2020

Normal brain function is associated with an assortment of oscillations of various frequencies, each reflecting the timing of separate computational processes and levels of synchronization within and between brain areas. Stimulation accurately delivered on a specified phase of a given oscillation provides the opportunity to target individual aspects of brain function. To achieve this, we have developed a highly responsive system to produce a continuous online phase-estimate. In addition to stable oscillations, the system accurately tracks the early cycles of short, transient oscillations and can operate across the frequency range of most established neuronal oscillations (4 to 250 Hz). Here we demonstrate bidirectional modulation of the pathologically elevated parkinsonian beta-band oscillation (around 35 Hz) in 6-OHDA hemi-lesioned rats. Beta phase, monitored using a single channel electrocorticogram above secondary motor cortex, was used to drive electrical stimulation of the globus pallidus on one of eight phases spanning the oscillation cycle. Stimulation of the early ascending phase suppressed the oscillation whereas stimulation of the early descending phase was amplifying. By implementing a rule that prevented stimulation when the phase estimate was unstable, we achieved a system that could adapt stimulation rate and pattern to respond to the changes produced in the target oscillation. This allowed the electronic system to create and maintain a state of equilibrium with the biological system resulting in continuous stable modulation of the target oscillation over time. These results demonstrate the feasibility of phase locked stimulation as a more refined strategy for remediation of pathological beta oscillations in the treatment of the motor symptoms of Parkinson’s disease. Furthermore, they establish the utility of our algorithm and allow for the potential to assess the contribution of rhythmic activity in neuronal computation across a number of brain systems.
Maternal approach behaviors toward neonatal calls are impaired by mother’s experiences of raising pups with a risk gene variant for autism
Authors: Kato Risa , Machida Akihiro , Nomoto Kensaku , Kang Gina , Hiramoto Takeshi , Tanigaki Kenji , Mogi Kazutaka , Hiroi Noboru , Kikusui Takefumi
Published: May 2020

How the intrinsic sequence structure of neonatal mouse pup ultrasonic vocalization (USV) and maternal experiences determine maternal behaviors in mice is poorly understood. Our previous work showed that pups with aTbx1heterozygous (HT) mutation, a genetic risk for autism spectrum disorder (ASD), emit altered call sequences that do not induce maternal approach behaviors in C57BL6/J mothers. Here, we tested how maternal approach behaviors induced by wild-type and HT USVs are influenced by the mother’s experience in raising pups of these two genotypes. The results showed that wild-type USVs were effective in inducing maternal approach behaviors when mothers raised wild-type but not HT pups. The USVs of HT pups were ineffective regardless of whether mothers raised HT or wild-type pups. However, the sequence structure of pup USVs had no effect on the general, non-directional incentive motivation of maternal behaviors. Our data show how the mother’s experience with a pup with a genetic risk for ASD alters the intrinsic incentive values of USV sequences in maternal approach behaviors.
Optogenetic activation of the inhibitory nigro-collicular circuit evokes orienting movements in mice
Authors: Villalobos C.A. , Basso M.A.
Published: May 2020

In contrast to predictions from the current model of basal ganglia (BG) function, we report here that increasing inhibition from the BG to the superior colliculus (SC) through the substantia nigra (nigra) using in vivo optogenetic activation of GABAergic terminals in mice, produces contralateral orienting movements. Orienting movements resulting from activation of inhibitory nigral terminals are unexpected because decreases and not increases, in nigral activity are generally associated with orienting movements. To determine how orienting movements may result from activation of inhibitory terminals, we performed a series of slice experiments and found that the same optogenetic stimulation of nigral terminals used in vivo, evoked post-inhibitory rebound depolarization and spiking in SC output neurons in vitro. Only high frequency (100Hz) stimulation evoked contralateral movements in vivo and triggered rebound spiking in vitro. The latency of orienting movements relative to the stimulation in vivo was similar to the latency of rebound spiking in vitro. Taken together, our results point toward a novel hypothesis that inhibition from the BG may play an active rather than passive role in the generation of orienting movements in mice.
What influences selection of native phosphorelay architectures?
Authors: Alves Rui , Salvado Baldiri , Milo Ron , Vilaprinyo Ester , Sorribas Albert
Published: May 2020

Phosphorelays are signal transduction circuits that combine four different phosphorylatable protein domains for sensing environmental changes and use that information to adjust cellular metabolism to the new conditions in the milieu. Five alternative circuit architectures account for more than 99% of all phosphorelay operons annotated in over 9000 fully sequenced genomes, with one of those architectures accounting for more than 72% of all cases.

Here we asked if there are biological design principles that explain the selection of preferred phosphorelay architectures in nature and what might those principles be. We created several types of data-driven mathematical models for the alternative phosphorelay architectures, exploring the dynamic behavior of the circuits in concentration and parameter space, both analytically and through over 108numerical simulations. We compared the behavior of architectures with respect to signal amplification, speed and robustness of the response, noise in the response, and transmission of environmental information to the cell.

Clustering analysis of massive Monte Carlo simulations suggests that either information transmission or metabolic cost could be important in selecting the architecture of the phosphorelay. A more detailed study using models of kinetically well characterized phosphorelays (Spo0 ofBacillus subtilisand Sln1-Ypd1-Ssk1-Skn7 ofSaccharomyces cerevisiae) shows that information transmission is maximized by the natural architecture of the phosphorelay. In view of this we analyze seventeen additional phosphorelays, for which protein abundance is available but kinetic parameters are not. The architectures of 16 of these are also consistent with maximization of information transmission.

Our results highlight the complexity of the genotype (architecture, parameter values, and protein abundance) to phenotype (physiological output of the circuit) mapping in phosphorelays. The results also suggest that maximizing information transmission through the circuit is important in the selection of natural circuit genotypes.
Systemic and mucosal antibody secretion specific to SARS-CoV-2 during mild versus severe COVID-19
Authors: Cervia Carlo , Nilsson Jakob , Zurbuchen Yves , Valaperti Alan , Schreiner Jens , Wolfensberger Aline , Raeber Miro E. , Adamo Sarah , Emmenegger Marc , Hasler Sara , Bosshard Philipp P. , De Cecco Elena , Bächli Esther , Rudiger Alain , Stüssi-Helbling Melina , Huber Lars C. , Zinkernagel Annelies S. , Schaer Dominik J. , Aguzzi Adriano , Held Ulrike , Probst-Müller Elsbeth , Rampini Silvana K. , Boyman Onur
Published: May 2020

Background

Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an acute illness termed coronavirus disease 2019 (COVID-19). Humoral immune responses likely play an important role in containing SARS-CoV-2, however, the determinants of SARS-CoV-2-specific antibody responses are unclear.

Methods

Using immunoassays specific for the SARS-CoV-2 spike protein, we determined SARS-CoV-2-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) in sera and mucosal fluids of two cohorts, including patients with quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR)-confirmed SARS-CoV-2 infection (n = 56; median age 61 years) with mild versus severe COVID-19, and SARS-CoV-2-exposed healthcare workers (n = 109; median age 36 years) with or without symptoms and tested negative or positive by RT-qPCR.

Findings

On average, SARS-CoV-2-specific serum IgA titers in mild COVID-19 cases became positive eight days after symptom onset and were often transient, whereas serum IgG levels remained negative or reached positive values 9–10 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum IgA and IgG titers as a function of duration since symptom onset, independent of patient age and comorbidities. Very high levels of SARS-CoV-2-specific serum IgA correlated with severe acute respiratory distress syndrome (ARDS). Interestingly, some of the SARS-CoV-2-exposed healthcare workers with negative SARS-CoV-2-specific IgA and IgG serum titers had detectable SARS-CoV-2-specific IgA antibodies in their nasal fluids and tears. Moreover, SARS-CoV-2-specific IgA levels in nasal fluids of these healthcare workers were inversely correlated with patient age.

Interpretation

These data show that systemic IgA and IgG production against SARS-CoV-2 develops mainly in severe COVID-19, with very high IgA levels seen in patients with severe ARDS, whereas mild disease may be associated with transient serum titers of SARS-CoV-2-specific antibodies but stimulate mucosal SARS-CoV-2-specific IgA secretion. The findings suggest four grades of antibody responses dependent on COVID-19 severity.
Confidence Sets for Cohen’sdEffect Size Images
Authors: Bowring Alexander , Telschow Fabian , Schwartzman Armin , Nichols Thomas E.
Published: May 2020

Current statistical inference methods for task-fMRI suffer from two fundamental limitations. First, the focus is solely on detection of non-zero signal or signal change, a problem that is exasperated for large scale studies (e.g. UK Biobank,N= 40, 000+) where the ‘null hypothesis fallacy’ causes even trivial effects to be determined as significant. Second, for any sample size, widely used cluster inference methods only indicate regions where a null hypothesis can be rejected, without providing any notion of spatial uncertainty about the activation. In this work, we address these issues by developing spatial Confidence Sets (CSs) on clusters found in thresholded Cohen’sdeffect size images. We produce an upper and lower CS to make confidence statements about brain regions where Cohen’sdeffect sizes have exceeded and fallen short of anon-zerothreshold, respectively. The CSs convey information about the magnitude and reliability of effect sizes that is usually given separately in at-statistic and effect estimate map. We expand the theory developed in our previous work on CSs for %BOLD change effect maps (Bowring et al., 2019) using recent results from the bootstrapping literature. By assessing the empirical coverage with 2D and 3D Monte Carlo simulations resembling fMRI data, we find our method is accurate in sample sizes as low asN= 60. We compute Cohen’sdCSs for the Human Connectome Project working memory taskfMRI data, illustrating the brain regions with a reliable Cohen’sdresponse for a given threshold. By comparing the CSs with results obtained from a traditional statistical voxelwise inference, we highlight the improvement in activation localization that can be gained with the Confidence Sets.