bluuebunny/crossref_metadata_2025 huggingface dataset:
Department Versus Division: An In-Depth Analysis of Units of Plastic Surgery and Other Surgical Specialties at Their Institutions
Authors: Murphy Alexander I. , Mellia Joseph A. , Diatta Fortunay , Mauch Jaclyn T. , Asadourian Paul A. , Christopher Adrienne N. , Azoury Saïd C. , Fischer John P.
Published: September 2021

An increasing number of plastic and reconstructive surgery (PRS) units have transitioned from divisions to departments in recent years. This study aimed to identify quantifiable differences that may reflect challenges and benefits associated with each type of unit. We conducted a cross-sectional analysis of publicly-available data on characteristics of academic medical institutions housing PRS units, faculty size of surgical units within these institutions, and academic environments of PRS units themselves. Univariate analysis compared PRS divisions versus departments. Matched-paired testing compared PRS units versus other intra-institutional surgical departments. Compared to PRS divisions (n = 64), departments (n = 22) are at institutions with more surgical departments overall (P = 0.0071), particularly departments that are traditionally divisions within the department of surgery (ie urology). Compared to PRS divisions, PRS departments have faculty size that more closely resembles other intra-institutional surgical departments, especially for full-time surgical faculty and faculty in areas of clinical overlap with other departments like hand surgery. Plastic and reconstructive surgery departments differ from PRS divisions by certain academic measures, including offering more clinical fellowships (P = 0.005), running more basic science laboratories (P = 0.033), supporting more nonclinical research faculty (P = 0.0417), and training residents who produce more publications during residency (P = 0.002). Institutions with PRS divisions may be less favorable environments for surgical divisions to become departments, but other recently-transitioned divisions could provide blueprints for PRS to follow suit. Bolstering full-time surgical faculty numbers and faculty in areas of clinical overlap could be useful for PRS divisions seeking departmental status. Transitioning to department may yield objective academic benefits for PRS units.
The Perception of Esthetic Importance of Craniofacial Elements
Authors: van Cruchten Cas , Feijen Michelle Marlena Wilhelmina , van der Hulst Rene Remmelt Willie Johan
Published: September 2021

The human face is an important human structure, often judged by its esthetics. It serves great purpose, as it is and always has been involved in both cultural matters, such as art, as well as biological matters, such as exhibition of emotion and mate selection. Throughout history, there have been multiple studies on what makes a face attractive. Despite the myriad ways in which the face has been explored academically, there has been a lack of reports on which craniofacial elements are deemed the most important for attractiveness subjectively. To fill up this gap on the perception of the esthetics of the human face, as well as to provide a contemporary view on the matter, this research was conducted. Participants were asked to fill out a questionnaire with a visual analogue scale for each craniofacial element and questions about appearance satisfaction. A total of 299 participants were enrolled in this study. Eyes, hair and teeth were deemed to be the most important craniofacial elements for attractiveness. Women scored teeth, hair, and eyebrows significantly higher than men, men scored higher in satisfaction with their own appearance than women. Older people, married people and people in a relationship care less about the opinion of others regarding their appearance. The results from this study can be used to identify a focus in the future development of esthetically related matters, such as plastic surgery or art and will add to the academic knowledge on the perception of craniofacial beauty.
Overcorrection of Nasal Bone Fracture Reduction Can Be Minimized by Packing Removal
Authors: Hwang Kun , Ma Sung Hwan
Published: September 2021

We experienced 16 cases of overcorrection among 524 cases of packing following nasal bone fracture (NBF) reduction. In these cases, the packing was removed immediately.

From July 2017 to October 2020, 535 cases of NBF were reduced by closed reduction. Nasal packing was applied in 524 cases (97.9%). In all cases, postoperative X-rays (both nasal bone lateral view and Water's view) were taken. The degree of overcorrection was measured in the nasal bone lateral views.

Among the 524 patients who underwent nasal packing, overcorrection was noted in 16 cases (3.1%). The average degree of overcorrection was 2.09 ± 0.70 mm. In these patients, the packing was removed immediately and X-rays were taken directly after packing removal. The degree of overcorrection decreased; however, no significant difference was found (1.83 ± 0.71 mm, P 
= 0.081, [paired t test]).

In this study, overcorrection was noted in 3.1% of patients in whom nasal packing was applied. After packing removal, the degree of overcorrection decreased but was not significant. Postoperative X-rays should be taken after reduction of NBF and nasal packing, and if overcorrection is noticed, the packing should be removed immediately.
Reconstruction of Medial Canthal Defects by Local/Loco-Regional Flaps
Authors: Bhandari Padam Singh
Published: September 2021

Aim:

To describe a series of medial canthal defect reconstruction by local/loco-regional flaps following excision of basal cell carcinoma.

Material and methods:

A series of 35 medial canthal defects following excision of basal cell carcinoma was reconstructed by local/loco-regional flaps. For smaller defects, glabellar lateral advancement flap or Limberg's flap from the nasolabial area were used to resurface the defects. For larger defects extending to the upper and lower eyelid or to the nose, a combination of flaps, that is, forehead and cheek rotation flaps or glabellar and cheek rotation flaps were used.

Result:

In all the cases, the aesthetic and functional results were highly satisfactory except in one, where punctum and lower canaliculi were also excised with the tumor for clearance. This patient complained of watering from the affected eye. Two patients had developed webbing after the operation. It was corrected by Z plasty after 6 months.

Conclusion:

Medial canthal defects are best managed by local/ loco-regional flaps. For smaller defects in the upper part, the glabellar flap is the choice of the flap and in the lower part, flaps from the nasolabial region give the best result. For larger defects not amenable to single flap, a combination of flaps (glabellar/forehead flap and cheek rotation flap) can close the defects with the good aesthetic and functional results.
The Utility of Quantitative EEG in Detecting Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage
Authors: Baang Hae Young , Chen Hsin Yi , Herman Alison L. , Gilmore Emily J. , Hirsch Lawrence J. , Sheth Kevin N. , Petersen Nils H. , Zafar Sahar F. , Rosenthal Eric S. , Westover M. Brandon , Kim Jennifer A.
Published: September 2021

In this review, we discuss the utility of quantitative EEG parameters for the detection of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage in the context of the complex pathophysiology of DCI and the limitations of current diagnostic methods. Because of the multifactorial pathophysiology of DCI, methodologies solely assessing blood vessel narrowing (vasospasm) are insufficient to detect all DCI. Quantitative EEG has facilitated the exploration of EEG as a diagnostic modality of DCI. Multiple quantitative EEG parameters such as alpha power, relative alpha variability, and alpha/delta ratio show reliable detection of DCI in multiple studies. Recent studies on epileptiform abnormalities suggest that their potential for the detection of DCI. Quantitative EEG is a promising, continuous, noninvasive, monitoring modality of DCI implementable in daily practice. Future work should validate these parameters in larger populations, facilitated by the development of automated detection algorithms and multimodal data integration.
Spectrograms for Seizure Detection in Critically Ill Children
Authors: Lalgudi Ganesan Saptharishi , Hahn Cecil D.
Published: September 2021

Electrographic seizures are common in critically ill children and a significant proportion of these seizures are nonconvulsive. There is an association between electrographic seizures and neurophysiological disturbances, worse short- and long-term neurologic outcomes, and mortality in critically ill patients. In this context, timely diagnosis and treatment of electrographic seizures in critically ill children becomes important. However, most institutions lack the resources to support round-the-clock or frequent review of continuous EEG recordings causing significant delays in seizure diagnosis. Given the current gaps in review of continuous EEG across institutions globally, use of visually simplified, time-compressed quantitative EEG trends such as spectrograms has the potential to enhance timeliness of seizure diagnosis and treatment in critically ill children.
Predictive Value of Multimodality Intraoperative Neurophysiological Monitoring During Cardiac Surgery
Authors: Thirumala Parthasarathy D. , Ahmad Akram I. , Roy Priya P. , Balzer Jeffrey R. , Crammond Donald J. , Anetakis Katherine M. , Fleseriu Cara M. , Subramaniam Kathirvel , Jadhav Ashutosh P. , Kilic Arman , Gleason Thomas
Published: September 2021

Introduction:

This study aimed to determine the ability of multimodality intraoperative neurophysiologic monitoring, including somatosensory evoked potentials (SSEP) and EEG, to predict perioperative clinical stroke and stroke-related mortality after open-heart surgery in high-risk patients.

Methods:

The records of all consecutive patients who underwent coronary artery bypass grafting, and cardiac valve repair/replacement with high risk for stroke who underwent both SSEP and EEG recording at the University of Pittsburgh Medical Center between 2009 and 2015 were reviewed. Sensitivity and specificity of these modalities to predict in-hospital clinical strokes and stroke-related mortality were calculated.

Results:

A total of 531 patients underwent open cardiac procedures monitored using SSEP and EEG. One hundred thirty-one patients (24.67%) experienced significant changes in either modality. Fourteen patients (2.64%) suffered clinical strokes within 24 hours after surgery, and eight patients (1.50%) died during their hospitalization. The incidence of in-hospital clinical stroke and stroke-related mortality among patients who experienced a significant change in monitoring compared with those with no significant change was 11.45% versus 1.75%. The sensitivity and specificity of significant changes in either SSEP or EEG to predict in-hospital major stroke and stroke-related mortality were 0.93 and 0.77, respectively.

Conclusions:

Intraoperative neurophysiologic monitoring with SSEP and EEG has high sensitivity and specificity in predicting perioperative stroke and stroke-related mortality after open cardiac procedures. These results support the benefits of multimodality neuromonitoring during cardiac surgery.
Electromyography in Congenital Zika Syndrome
Authors: Gouveia de Melo Ana C. M. , van der Linden Vanessa , Serpa Sarah C. , Rolim Filho Epitácio L. , Lins Otávio G.
Published: September 2021

Introduction:

Congenital Zika virus syndrome is a distinct pattern of birth defects in fetuses infected by the Zika virus. It presents a broad clinical spectrum that includes occurrences of microcephaly, hypertonia, dysphagia, hyperexcitability, seizures, and arthrogryposis. Imaging findings show neuronal migration disorders.

Methodology:

Case reports have suggested that arthrogryposis has a neurogenic cause. We analyzed needle electromyography and nerve conduction examinations on 77 patients aged 2–24 months presenting highly probable congenital Zika virus syndrome, with or without arthrogryposis.

Results:

All those with arthrogryposis presented with chronic muscle denervation in the electromyography examination. Similarly, children with single or reversible joint abnormalities at birth showed the same findings. Denervation in the paravertebral musculature was found in all of the children with diaphragmatic paralysis or thoracic deformities.

Conclusions:

We propose that congenital contractures associated with congenital Zika virus syndrome are caused by the malformation of upper and lower motor neurons during embryogenesis.
Spectrum of Ictal–Interictal Continuum: The Significance of 2HELPS2B Score and Background Suppression
Authors: Lee Dong Ah , Park Kang Min , Kim Hyung Chan , Khoo Ching Soong , Lee Byung In , Kim Sung Eun
Published: September 2021

Purpose:

The aims of this study were to identify (1) the spectrum of ictal–interictal continuum (IIC) using the two dimensions of 2HELPS2B score and background suppression and (2) the response to subsequent anti-seizure drugs depends on the spectrum of IIC.

Methods:

The study prospectively enrolled 62 patients with IIC on EEG. The diagnosis of nonconvulsive status epilepticus was attempted with Salzburg criteria as well as clinical and neuroimaging data. IICs were dichotomized into patients with nonconvulsive status epilepticus and coma-IIC. The 2HELPS2B score was evaluated as the original proposal. The suppression ratio was analyzed with Persyst software.

Results:

Forty-seven cases (75.8%) were nonconvulsive status epilepticus-IIC and 15 cases (24.2%) were coma-IIC. Multivariate analysis revealed that the 2HELPS2B score was the only significant variable dichotomizing the spectrum of IIC (odds ratio, 3.0; 95% confidence interval, 1.06–8.6; P = 0.03 for nonconvulsive status epilepticus-IIC). In addition, the suppression ratio was significantly negatively correlated with 2HELPS2B scores (Spearman coefficient = −0.37, P = 0.004 for left hemisphere and Spearman coefficient = −0.3, P = 0.02 for right hemisphere). Furthermore, patients with higher 2HELPS2B score (74% [14/19] in ≥2 points vs. 44% [14/32] in <2 points, P = 0.03 by χ2 test) and lower suppression ratio (62% [23/37] in ≤2.18 vs. 35% [6/17] in >2.18, P = 0.06 by χ2 test) seemed to be more responsive to subsequent anti-seizure drug.

Conclusions:

The 2HELPS2B score and background suppression can be used to distinguish the spectrum of IIC and thereby predict the response to subsequent anti-seizure drug.
Genome sequencing as a first-line diagnostic test for hospitalized newborns
Authors: Bowling Kevin M. , Thompson Michelle L. , Finnila Candice R. , Hiatt Susan M. , Latner Donald R. , Amaral Michelle D. , Lawlor James M.J. , East Kelly M. , Cochran Meagan E. , Greve Veronica , Kelley Whitley V. , Gray David E. , Felker Stephanie A. , Meddaugh Hannah , Cannon Ashley , Luedecke Amanda , Jackson Kelly E. , Hendon Laura G. , Janani Hillary M. , Johnston Marla , Merin Lee Ann , Deans Sarah L. , Tuura Carly , Williams Heather , Laborde Kelly , Neu Matthew B. , Patrick-Esteve Jessica , Hurst Anna C.E. , Kandasamy Jegen , Carlo Wally , Brothers Kyle B. , Kirmse Brian M. , Savich Renate , Superneau Duane , Spedale Steven B. , Knight Sara J. , Barsh Gregory S. , Korf Bruce R. , Cooper Gregory M.
Published: September 2021

Purpose

SouthSeq, a translational research study to perform genome sequencing (GS) for infants with symptoms suggestive of a genetic disorder, was conducted in NICUs in the Southeastern US. Recruitment targeted racial/ethnic minorities and rural, medically underserved areas that are historically under-represented in genomic medicine research.

Methods

GS and analysis were performed for 367 newborns to detect disease-causal genetic variation concurrent with standard of care evaluation and testing.

Results

Definitive diagnostic (DD) or likely diagnostic (LD) genetic findings were identified in 30% of newborns and 14% harbored an uncertain result. Only 39% of DD/LD findings were identified via concurrent standard of care suggesting that GS testing is better for obtaining early genetic diagnosis. We also identified phenotypes that correlate with the likelihood of receiving a DD/LD finding, such as craniofacial, ophthalmologic, auditory, skin, and hair abnormalities. We did not observe any differences in diagnostic rates between racial/ethnic groups.

Conclusion

We describe one of the largest to-date GS cohorts of ill newborns, enriched for African American and rural patients. Our results demonstrate the utility of GS as it provides early in life detection of clinically relevant genetic variation not identified via current standard clinical testing, particularly for newborns exhibiting certain phenotypic features.
Huntington’s Disease Integrated Staging System (HD-ISS): A Novel Evidence-Based Classification System For Staging
Authors: Tabrizi Sarah J. , Schobel Scott , Gantman Emily C. , Mansbach Alexandra , Borowsky Beth , Konstantinova Pavlina , Mestre Tiago A. , Panagoulias Jennifer , Ross Christopher A. , Zauderer Maurice , Mullin Ariana P. , Romero Klaus , Sivakumaran Sudhir , Turner Emily C. , Long Jeffrey D. , Sampaio Cristina
Published: September 2021

Background

Despite the monogenic autosomal dominant nature of Huntington’s disease (HD), the current research paradigm is still based on overt clinical phenotypes and does not address disease pathobiology and biomarkers that are evident decades before functional decline. A new research framework is needed to standardize clinical research and enable interventional studies earlier in the course of HD.

Methods

The HD Regulatory Science Consortium (HD-RSC), a precompetitive Critical Path Institute initiative that includes 37 member organizations, created the Regulatory Science Forum working group (RSF), which includes industry and academic representatives. To generate a new evidenced-based HD Integrated Staging System (HD-ISS) using a formal consensus methodology, the RSF considered prognostic biomarkers, signs, and symptoms of HD, and performed empirical data analysis. We used observational data to calculate healthy-control-based landmark variable cut-offs for Stage classification and to internally validate the framework.

Findings

The HD-ISS starts with Stage 0, which comprises individuals with ≥ 40 cytosine-adenine-guanine repeats (CAG) in the huntingtin gene (HTT), before detectable indications of disease. We concluded that detectable HD progression is verified with measurable indicators of underlying pathophysiology (Stage 1), proceeds to a detectable clinical phenotype (Stage 2), and continues to a decline in function (Stage 3). Operationally, individuals can be unambiguously classified into Stages 1-3 based on CAG-independent thresholds of landmark assessments. Both cross-sectional status and longitudinal HD-ISS Stage progress align with HD natural history, and Stage transitions accelerate as CAG increase.

Interpretation

The HD-ISS encompasses the full course of HD starting at birth, defined by the presence of the genetic expansion. This new framework aims to standardize language for clinical research and its immediate use will enable further validation. The HD-ISS provides structure to harmonize clinical study populations and facilitates the clinical assessment of interventions earlier in HD to prevent or slow disease progression.

Funding

CHDI Foundation Inc.
On-scalp magnetoencephalography for childhood epilepsies
Authors: Feys Odile , Corvilain Pierre , Aeby Alec , Sculier Claudine , Christiaens Florence , Holmes Niall , Brookes Matthew , Goldman Serge , Wens Vincent , De Tiège Xavier
Published: September 2021

Magnetoencephalography (MEG) is an established method to investigate epilepsy. Current MEG systems house hundreds of cryogenic sensors in a rigid, one-size-fits-all helmet, which results in several limitations, particularly in children. On-scalp MEG based on optically-pumped magnetometers (OPMs) may alleviate these limitations.

We report on five children (5–11 years old) with self-limited focal (n=3) or structural (n=2) epilepsy who underwent cryogenic (102 magnetometers) and on-scalp (32 OPMs) MEG. We compared the two modalities for the detection and localization of interictal epileptiform discharges (IEDs).

We identified IEDs in all children with comparable sensor topographies for both MEG devices. IED amplitudes were 2.3-4.8 times higher with on-scalp MEG and signal-to-noise ratio (SNR) was also 27-60% higher with on-scalp MEG in all but one patient with large head movement artifacts. The neural source of averaged IEDs was located at about 5 mm (n=3) or higher (8.3 mm, n=1; 15.6 mm, n=1) between on-scalp and cryogenic MEG.

Despite limited number of sensors and scalp coverage, on-scalp MEG detects IEDs in epileptic children with higher SNR than cryogenic MEG. This technology, which is in constant development, should become a reference in the diagnostic workup of epilepsy and replace cryogenic MEG in the near future.
Airway management, procedural data, and mortality records of patients undergoing surgery for mucormycosis associated with coronavirus disease (COVID-19)
Authors: Sirohiya Prashant , Vig Saurabh , Mathur Tanmay , Meena Jitendra Kumar , Panda Smriti , Goswami Gitartha , Gupta Raghav , konkimalla Abhilash , Kondamudi Dheeraj , Gupta Nishkarsh , Ratre Brajesh Kumar , Singh Ram , Kumar Balbir , Pandit Anuja , Sikka Kapil , Thakar Alok , Bhatnagar Sushma
Published: September 2021

Purpose

Although unexpected airway difficulties are reported in patients with mucormycosis, the literature on airway management in patients with mucormycosis associated with Coronavirus disease is sparse.

Methods

In this retrospective case record review of 57 patients who underwent surgery for mucormycosis associated with coronavirus disease, we aimed to evaluate the demographics, airway management, procedural data, and mortality records.

Results

Forty-one (71.9%) patients had a diagnosis of sino-nasal mucormycosis, fourteen (24.6%) patients had a diagnosis of rhino-orbital mucormycosis, and 2 (3.5%) patients had a diagnosis of palatal mucormycosis. A total of 44 (77.2%) patients had co-morbidities. The most common co-morbidities were diabetes mellitus in 42 (73.6%) patients, followed by hypertension in 21 (36.8%) patients, and acute kidney injury in 14 (28.1%) patients. We used the intubation difficulty scale score to assess intubating conditions. Intubation was easy to slightly difficult in 53 (92.9%) patients. In our study, mortality occurred in 7 (12.3%) patients. The median (range) mortality time was 60 (27–74) days. The median (range) time to hospital discharge was 53.5 (10–85) days. The median [interquartile range] age of discharged versus expired patients was 47.5 [41,57.5] versus 64 [47,70] years (P = 0.04), and median (interquartile range) D-dimer levels in discharged versus expired patients was 364 [213, 638] versus 2448 [408,3301] ng/mL (P = 0.03).

Conclusion

In patients undergoing surgery for mucormycosis associated with the coronavirus disease, airway management was easy to slightly difficult in most patients. Perioperative complications can be minimized by taking timely and precautionary measures.
Analysis of the prediction of the 2021 time-evolution of the Covid-19 Pandemic in Italy using a Planck’s distribution
Authors: Ciufolini Ignazio , Paolozzi Antonio
Published: September 2021

In a previous paper we studied the time evolution of the Covid-19 pandemic in Italy during the first wave of 2020 using a number of distribution laws. We concluded that the best distribution law to predict the evolution of the pandemic, if basic conditions of the pandemic (such as distancing measures, use of masks, start of schools, intensive use of public transportation, beginning and end of holidays, vaccination campaign and no significant onset of new Covid variants) do not appreciably change, is a distribution of the type of Planck’s law with three parameters. In our 2020 study we did not use the number of daily positive cases in Italy but the ratio of daily positive cases per number of daily tests, ratio today sometimes referred to as: “positivity rate”. We showed that, if basic conditions do not change, the Planck’s distribution with three parameters provides very good predictions of the positivity rate about one month in advance. In particular, in a second paper, using the Planck’s distribution with three parameters, we predicted, about one month in advance, the spread of the pandemic in Italy during the Christmas 2020 holidays with an error of a few percent only. We then study the present (September 2021) evolution of the pandemic in Italy and we show that the Planck’s distribution, based on the data of July and August, predicts well the evolution of the pandemic. In particular, we show that the peak of the positivity rate was predicted to occur approximately around the middle of August and that the agreement of this Planck’s function (obtained fitting the data up to 10 July 2021) and the positivity rate observed after 5 weeks, on 12 September 2021 is very good. However, the end of the Italian holidays and the start of all the activities including schools, intensive use of public transportation and further changes in distancing measures may cause a discrepancy of the predicted trend of the positivity rate of the pandemic with respect to the real observed values.
Change in Measles Vaccine Coverage and Estimated Impact on Measles Mortality in Low and Middle Income Countries, 2020: An Investigation into Secondary Public Health Effects of the COVID-19 Pandemic Using the Lives Saved Tool
Authors: Gregory Lucy
Published: September 2021

With the global COVID-19 pandemic, many public health services were severely disrupted. Estimating the overall health effects of this is difficult as most disease surveillance systems have also been substantially affected during the pandemic. For some diseases, this effect is mitigated by the methods enacted to fight the pandemic, such as use of facial coverings, social distancing and quarantine, but measles is infectious to the degree that this mitigation is likely to be limited. Thus, outbreaks and an increase in global measles mortality are expected. However, the severity of this impact is not yet known.

In early 2020, a study by Roberton and colleagues predicted an additional 12,360 to 37,920 deaths in children under-five worldwide from measles over the coming year based on three potential levels of vaccine coverage reductions ranging from 18.5 to 51.9%. Our study investigates the magnitude of the increase in measles mortality due to decreased vaccine coverage because of COVID-19, based on official estimates of 2020 measles vaccine coverage from WHO/UNICEF released in July 2021. Using the Lives Saved Tool (LiST), an interventions modeling program, we estimated measles mortality for low/middle income countries (LMICs) based on the 2020 WHO/UNICEF estimates of national immunization coverage (WUENIC). Because these calculations use actual reported vaccine coverage, they provide a more accurate picture of measles mortality related to COVID-19 disruptions in 2020.

Using the WUENIC data, LiST predicted fewer additional deaths in 2020 due to decreases in measles vaccine coverage than estimations made by LiST based on Roberton, 2020 due to remarkable recovery efforts by national immunization programmes in the second half of 2020.
Race and Ethnic Group Dependent Space Radiation Cancer Risk Predictions
Authors: Cucinotta Francis A. , Saganti Premkumar B.
Published: September 2021

Future space missions by national space agencies and private industry, including space tourism, will include a diverse makeup of crewmembers with extensive variability in age, sex, and race or ethnic groups. The relative risk (RR) model is used to transfer epidemiology data between populations to estimate radiation risks. In the RR model cancer risk is assumed to be proportional to background cancer rates and limited by other causes of death, which are dependent on genetic, environmental and dietary factors that are population dependent. Here we apply the NSCR-2020 model to make the first predictions of age dependent space radiation cancer risks for several U.S. populations, which includes Asian-Pacific Islanders (API), Black, Hispanic (white and black), and White (non-Hispanic) populations. Results suggest that male API and Hispanic populations have the overall lowest cancer risks, while White females have the highest risk. Blacks have similar total cancer rates as Whites, however their reduced life expectancy leads to modestly lower lifetime radiation risks compared to Whites. There are diverse tissue specific cancer risk ranking across sex and race, which include sex specific organ risks, females having larger lung, stomach, and urinary-bladder radiation risks, and males having larger colon and brain risks.
Nationwide trends in COVID-19 cases and SARS-CoV-2 wastewater concentrations in the United States
Authors: Duvallet Claire , Wu Fuqing , McElroy Kyle A. , Imakaev Maxim , Endo Noriko , Xiao Amy , Zhang Jianbo , Floyd-O’Sullivan Róisín , Powell Morgan M , Mendola Samuel , Wilson Shane T , Cruz Francis , Melman Tamar , Sathyanarayana Chaithra Lakshmi , Olesen Scott W. , Erickson Timothy B. , Ghaeli Newsha , Chai Peter , Alm Eric , Matus Mariana
Published: September 2021

Wastewater-based epidemiology has emerged as a promising technology for population-level surveillance of COVID-19 disease. The SARS-CoV-2 virus is shed in the stool of infected individuals and aggregated in public sewers, where it can be quantified to provide information on population-level disease incidence that is unbiased by access to clinical testing. In this study, we present results from the largest nationwide wastewater monitoring system in the United States reported to date. We profile 55 locations with at least six months of sampling and highlight their wastewater data from April 2020 through May 2021. These locations represent over 12 million individuals across 19 states. Samples were collected approximately weekly by wastewater treatment utilities as part of a regular wastewater surveillance service and analyzed for SARS-CoV-2 concentrations using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Concentrations of SARS-CoV-2 (copies/mL) were normalized to pepper mild mottle virus (PMMoV), a stable and persistent indicator of feces concentrations in wastewater. Here, we show that wastewater data reflects temporal and geographic trends in clinical COVID-19 cases, demonstrating that wastewater surveillance is a feasible approach for nationwide population-level monitoring of COVID-19 disease. We also provide key lessons learned from our broad-scale implementation of wastewater-based epidemiology, which can be used to inform wastewater-based epidemiology approaches for future emerging diseases. With an evolving epidemic and effective vaccines against SARS-CoV-2, wastewater-based epidemiology can serve as an important passive surveillance approach to detect changing dynamics or resurgences of the virus.

Highlights

We present results from a nationwide wastewater monitoring network in the United States, which represents one of the broadest temporal and geographic wastewater-based epidemiology datasets to-date.

Wastewater concentrations measured within individual locations reflect temporal trends in reported COVID-19 cases in the associated communities.

Wastewater concentrations also reflect geographic patterns in reported COVID-19 cases across states throughout the pandemic.

Normalizing wastewater concentrations to a fecal marker virus improves the correlation between wastewater data and clinical cases across locations but not necessarily over time within individual locations.

Implementing a nationwide wastewater monitoring system for SARS-CoV-2 is feasible, practical, and sustainable.
Robust immune response to the BNT162b mRNA vaccine in an elderly population vaccinated 15 months after recovery from COVID-19
Authors: Lee Hye Kyung , Knabl Ludwig , Knabl Ludwig , Kapferer Sebastian , Pateter Birgit , Walter Mary , Furth Priscilla A. , Hennighausen Lothar
Published: September 2021

Knowledge about the impact of prior SARS-CoV-2 infection of the elderly on mRNA vaccination response is needed to appropriately address the need for booster vaccination in this vulnerable population. To address this, we investigated antibody and genomic immune responses in 16 elderly (avg. 81 yrs.) individuals that had received a single booster dose of BNT162b vaccine 15 months after recovering from COVID-19. Spike-specific IgG antibody levels increased in each of the study participants from an average of 710 U/ml prior to the vaccination to more than 40,000 U/ml within ten weeks after the vaccination. In contrast, anti-spike-specific IgG antibody levels averaged 2,190 U/ml in 14 healthy SARS-CoV-2-naïve individuals (avg. 58 yrs.) ten weeks after the second dose of BNT162b. RNA-seq conducted on PBMCs demonstrated the activation of interferon-activated genetic programs in both cohorts within one day. Unlike their transient induction in the younger naïve population, persistent activity and the initiation of additional cell cycle regulated programs were obtained in the older COVID-19 recovered population. Here we show that the elderly, a high-risk population, can mount a strong antibody and a persistent molecular immune response upon receiving a single dose of mRNA vaccine 15 months after recovery from COVID-19.
Characterization of the secretome, transcriptome and proteome of human β cell line EndoC-βH1
Authors: Ryaboshapkina Maria , Saitoski Kevin , Hamza Ghaith M. , Jarnuczak Andrew F. , Berthault Claire , Sengupta Kaushik , Underwood Christina Rye , Andersson Shalini , Scharfmann Raphael
Published: September 2021

Early diabetes research is hampered by limited availability, variable quality and instability of human pancreatic islets in culture. Little is known about the human β cell secretome, and recent studies question translatability of rodent β cell secretory profiles. Here, we verify representativeness of EndoC-βH1, one of the most widely used human β cell lines, as a translational human β cell model based on omics and characterize the EndoC-βH1 secretome. We profiled EndoC-βH1 cells using RNA-seq, Data Independent Acquisition (DIA) and Tandem Mass Tag proteomics of cell lysate. Omics profiles of EndoC-βH1 cells were compared to human β cells and insulinomas. Secretome composition was assessed by DIA proteomics. Agreement between EndoC-βH1 cells and primary adult human β cells was ~90% for global omics profiles as well as for β cell markers, transcription factors and enzymes. Discrepancies in expression were due to elevated proliferation rate of EndoC-βH1 cells compared to adult β cells. Consistently, similarity was slightly higher with benign non-metastatic insulinomas. EndoC-βH1 secreted 671 proteins in untreated baseline state and 3,278 proteins when stressed with non-targeting control siRNA, including known β cell hormones INS, IAPP, and IGF2. Further, EndoC-βH1 secreted proteins known to generate bioactive peptides such as granins and enzymes required for production of bioactive peptides. Unexpectedly, exosomes appeared to be a major mode of secretion in EndoC-βH1 cells. We believe that secretion of exosomes and bioactive peptides warrant further investigation with specialized proteomics workflows in future studies.

Graphical abstract

Highlights

We validate EndoC-βH1 as a translational human β cell model using omics.

We present the first unbiased proteomics composition of human β cell line secretome.

The secretome of human β cells is more extensive than previously thought.

Untreated cells secreted 671 proteins and stressed cells secreted 3,278 proteins.

Secretion of exosomes and bioactive peptides constitute directions of future research.
LongPhase: an ultra-fast chromosome-scale phasing algorithm for small and large variants
Authors: Lin Jyun-Hong , Chen Liang-Chi , Yu Shu-Qi , Huang Yao-Ting
Published: September 2021

Long-read phasing has been used for reconstructing diploid genomes, improving variant calling, and resolving microbial strains in metagenomics. However, the phasing blocks of existing methods are broken by large Structural Variations (SVs), and the efficiency is unsatisfactory for population-scale phasing. This paper presents an ultra-fast algorithm, LongPhase, which can simultaneously phase single nucleotide polymorphisms (SNPs) and SVs of a human genome in ∼10-20 minutes, 10x faster than the state-of-the-art WhatsHap and Margin. In particular, LongPhase produces much larger phased blocks at almost chromosome level with only long reads (N50=26Mbp). We demonstrate that LongPhase combined with Nanopore is a cost-effective approach for providing chromosome-scale phasing without the need for additional trios, chromosome-conformation, and single-cell strand-seq data.
Identifying Microstructural Changes in Diffusion MRI; How to Circumvent Parameter Degeneracy
Authors: Rafipoor Hossein , Zheng Ying-Qiu , Griffanti Ludovica , Jbabdi Saad , Cottaar Michiel
Published: September 2021

Biophysical models that attempt to infer real-world quantities from data usually have many free parameters. This over-parameterisation can result in degeneracies in model inversion and render parameter estimation ill-posed. However, in many applications, we are not interested in quantifying the parameters per se, but rather in identifying changes in parameters between experimental conditions (e.g. patients vs controls). Here we present a Bayesian framework to make inference on changes in the parameters of biophysical models even when model inversion is degenerate, which we refer to as Bayesian EstimatioN of CHange (BENCH).

We infer the parameter changes in two steps; First, we train models that can estimate the pattern of change in the measurements given any hypothetical direction of change in the parameters using simulations. Next, for any pair of real data sets, we use these pre-trained models to estimate the probability that an observed difference in the data can be explained by each model of change.

BENCH is applicable to any type of data and models and particularly useful for biophysical models with parameter degeneracies, where we can assume the change is sparse. In this paper, we apply the approach in the context of microstructural modelling of diffusion MRI data, where the models are usually over-parameterised and not invertible without injecting strong assumptions.

Using simulations, we show that in the context of the standard model of white matter our approach is able to identify changes in microstructural parameters from conventional multi-shell diffusion MRI data. We also apply our approach to a subset of subjects from the UK-Biobank Imaging to identify the dominant standard model parameter change in areas of white matter hyperintensities under the assumption that the standard model holds in white matter hyperintensities.
Reproductive neuronal circuitry in adaptive changes of energy balance
Authors: Lee Pilhwa , de Miera Cristina Sáenz , Bellefontaine Nicole , Silveira Marina A , Zampieri Thais T , Donato Jose , Williams Kevin W. , Frazao Renata , Elias Carol F.
Published: September 2021

The crosstalk between metabolism and reproduction is essential for species survival. When dysfunctional, this interaction may decrease reproductive efficiency, but in physiological conditions of high energy demands, e.g., pregnancy and lactation, it is highly beneficial. Females display adaptive responses that assure offspring survival and health, including increased food intake and suppression of the reproductive function. Some of these physiological responses are modulated by leptin actions in neuronal pathways that are still unclear. The hypothalamic ventral premammillary nucleus (PMv) is a key integrative node of metabolic cues and reproductive status, comprised of either leptin-depolarized or -hyperpolarized neurons. Here, we show that the subset of leptin-hyperpolarized neurons coexpresses dopamine transporter (DAT) and prolactin receptor. DAT expression is higher in prepubertal conditions, when reproductive function is suppressed. These neurons innervate AgRP presynaptic terminals and may potentiate their inhibitory actions on reproduction. We further applied a mathematical model to reconcile our new findings with the current literature and to verify if those neurons are putative components of the metabolic control of reproduction. In our model, leptin-depolarized PMv neurons project to and directly stimulate kisspeptin and gonadotropin releasing hormone (GnRH) neurons. Leptin-hyperpolarized PMv DAT neurons are directly stimulated by prolactin and project to inhibitory control sites. During conditions of high prolactin levels, i.e., late pregnancy and lactation, this pathway may overcome the former, facilitating AgRP actions in the suppression of the reproductive function. Our model also predicts that overstimulation of this pathway may underlie earlier puberty and reproductive deficits observed in conditions of metabolic dysfunction.

Significance Statement

Women with excess or low energy stores (e.g., obesity or anorexia) have reproductive deficits, including altered puberty onset, disruption of reproductive cycles and decreased fertility. If able to conceive, they show higher risks of miscarriages and preterm birth. The hypothalamic circuitry controlling the interplay between metabolism and reproduction is undefined. Neurons in the ventral premammillary nucleus express leptin receptor and project to reproductive control sites. Those neurons are essentially glutamatergic, but functionally and phenotypically heterogeneous. They either depolarize or hyperpolarize in response to leptin. We show that leptin-hyperpolarized neurons coexpress dopamine transporter and prolactin receptor, and project to AgRP inhibitory output. Computational modeling was applied to build a neuronal network integrating metabolism and reproduction in typical and dysfunctional physiology.
Biogeographical patterns and diversity in the diet of the culpeo (Lycalopex culpaeus) in South America
Authors: Lozano Jorge , Guntiñas Marta , Cisneros Rodrigo , Llorente Esther , Malo Aurelio F.
Published: September 2021

Here we describe the dietary patterns of the culpeo (or Andean fox) at a biogeographical scale. We also analyze the influence of exotic lagomorphs on its diet and explore differences between culpeo subspecies. We selected 17 mutually comparable diet studies, which include 19 independent diet assessments. Then, we extracted and standardized the values of the different diet components from these studies and calculated the relative frequency of occurrence (RF) of the ten main trophic groups that we found. Further, we calculated the Shannon-Wienner H’ trophic diversity index.

The results showed that small mammals (41%), lagomorphs (21%), invertebrates (12.4%) and large herbivores (7.3%) were the most consumed groups. A factorial analysis of all trophic groups rendered four orthogonal factors that were used as response variables in relation to a set of environmental predictors. Altitude correlated with most factors (i.e. trophic groups). Exotic lagomorphs were consumed in lowlands, in higher latitudes and in regions showing high values of the human footprint index, replacing in these areas native fauna as the main prey. There were no differences in diet between the two main culpeo subspecies analysed, L.c. culpaeus and L.c. andinus.

Finally, the best explanatory models (GLM) of trophic diversity selected, using the Akaike’s information criterion (AIC), showed that the most diverse diets were those composed of large herbivores, edentates, carnivorous species, birds and herptiles (i.e. amphibians and reptils), in areas of high rainfall located in protected areas. Neither latitude nor altitude seemed to have an effect on the trophic diversity of the culpeos, as they were not retained by the final models.
A faithful in vivo model of human macrophages in metastatic melanoma
Authors: Voillet Valentin , Berger Trisha R. , McKenna Kelly M. , Paulson Kelly G. , Smythe Kimberly S. , Hunter Daniel S. , Valente William J. , Weaver Stephanie , Campbell Jean S. , Kim Teresa S. , Byrd David R. , Bielas Jason H. , Pierce Robert H. , Chapuis Aude G. , Gottardo Raphaël , Rongvaux Anthony
Published: September 2021

Abstract

Despite recent therapeutic progress, advanced melanoma remains lethal for many patients. The composition of the immune tumor microenvironment (TME) has decisive impacts on therapy response and disease outcome. High dimensional analyses of patient samples can reveal the composition and heterogeneity of the immune TME. In particular, macrophages are known for their cancer-supportive role, but the underlying mechanisms are incompletely understood, and experimental in vivo systems are needed to test the functional properties of these cells. We characterized a humanized mouse model, reconstituted with a human immune system and a human melanoma, in which: (1) human macrophages support metastatic spread of the tumor; and (2) tumor-infiltrating macrophages have a specific transcriptional signature that faithfully represents the transcriptome of macrophages from patient melanoma samples and is associated with shorter survival. This model complements patient sample analyses, enabling the elucidation of fundamental principles in melanoma biology, and the development and evaluation of candidate therapies.
Lateralized phenotypic differences after intrahippocampal kainic acid injection in female mice
Authors: Cutia Cathryn A. , Leverton Leanna K. , Ge Xiyu , Youssef Rana , Raetzman Lori T. , Christian-Hinman Catherine A.
Published: September 2021

Clinical evidence indicates that patients with temporal lobe epilepsy (TLE) often show differential outcomes of comorbid conditions in relation to the lateralization of the seizure focus. A particularly strong relationship exists between the side of seizure focus and the propensity for distinct reproductive endocrine comorbidities in women with TLE. Therefore, here we evaluated whether targeting of left or right dorsal hippocampus for intrahippocampal kainic acid (IHKA) injection, a model of TLE, produces different outcomes in hippocampal granule cell dispersion, body weight gain, and multiple measures of reproductive endocrine dysfunction in female mice. One, two, and four months after IHKA or saline injection, in vivo measurements of estrous cycles and weight were followed by ex vivo examination of hippocampal dentate granule cell dispersion, circulating ovarian hormone and corticosterone levels, ovarian morphology, and pituitary gene expression. IHKA mice with right-targeted injection (IHKA-R) showed greater granule cell dispersion and pituitary Fshb expression compared to mice with left-targeted injection (IHKA-L). By contrast, pituitary expression of Lhb and Gnrhr were higher in IHKA-L mice compared to IHKA-R, but these values were not different from respective saline-injected controls. IHKA-L mice also showed an increased rate of weight gain compared to IHKA-R mice. Increases in estrous cycle length, however, were similar in both IHKA-L and IHKA-R mice. These findings indicate that although major reproductive endocrine dysfunction phenotypes present similarly after targeting left or right dorsal hippocampus for IHKA injection, distinct underlying mechanisms based on lateralization of epileptogenic insult may contribute to produce similar emergent reproductive endocrine outcomes.

Highlights

Greater granule cell dispersion with right-sided IHKA injection

Changes in pituitary gene expression vary with side of injection

Increased weight gain after left-sided injection

Similar estrous cycle disruption after injection of left or right hippocampus