bluuebunny/crossref_metadata_2025 huggingface dataset:
Osteology and phylogeny of small-bodied hadrosauromorphs from an end-Cretaceous marine assemblage
Authors: Brownstein Chase Doran
Published: July 2020

The timing of non-avian dinosaur decline is one of the most debated subjects in dinosaur palaeontology. Dinosaur faunas from the last few million years of the Mesozoic appear far less diverse than those from earlier in the Cretaceous, a trend that could suggest non-avian dinosaur extinction occurred gradually. However, the limited nature of the latest Cretaceous dinosaur record outside western North America has obscured patterns in dinosaur diversity just before the extinction. Here, I describe two associated skeletons and several isolated fossils recovered from the New Egypt Formation of New Jersey, a latest Maastrichtian unit that underlies the K–Pg boundary. The larger skeleton appears to be a small-bodied adult from a lineage outside Hadrosauridae, the dominant group of these animals during the Maastrichtian, that persisted along the eastern coast of North America. Smaller specimens are identifiable as juvenile hadrosauromorphs. These results substantiate an important assemblage of herbivorous dinosaurs from the poorly-known Cretaceous of eastern North America. The marine depositional setting for these skeletons demonstrates that proposed ecosystem preferences among hadrosauromorphs may be biased by post-mortem transportation, and the adult skeleton has implications for assessing the proposed relictual nature of Late Cretaceous eastern North American vertebrates.
Spatiotemporal Distribution of Potato-AssociatedAlternariaSpecies in Wisconsin
Authors: Ding Shunping , Meinholz Kiana , Gevens Amanda J.
Published: July 2020

Potato early blight caused by Alternaria solani and potato brown spot caused by Alternaria alternata are two common potato foliar diseases. Fungicide applications in Wisconsin target early blight with the expectation of managing brown spot simultaneously. However, distributions of the two pathogens over time and space have not been previously reported in Wisconsin. In this study, six potato fields in Wisconsin were systematically sampled during 2014 to 2017 to investigate the incidences of both pathogens; incidences of the pathogens were compared by location, timing, and year. Incidence of A. alternata had been recorded starting in late June in every field every year, whereas incidence of A. solani started later in some of the fields. At the end of each growing season throughout the four years, the highest incidence (100% most of the years) of A. solani was observed in a field in Plover, located in a concentrated potato production area of central Wisconsin, and a field in Arena, located in an isolated potato production area in southern Wisconsin. The highest incidence (100% every year) of A. alternata was observed in a field in Madison, an isolated potato field that was managed organically. Such distribution patterns could be a result of the different host ranges of the pathogens and abundance of inoculum in different geographic locations. In 2016, disease severity was correlated with the incidence of both pathogens (P < 0.0001 to P = 0.0299), but in 2017, disease severity was correlated with the incidence of A. solani in most of the fields (P < 0.0001 to P = 0.0799). These findings suggest that both Alternaria spp. are important for considering disease management strategies in central and southern Wisconsin.
Complete Genome Sequence Resource of a Strain of Curtobacterium flaccumfaciens pv. flaccumfaciens, the Causal Agent of Bacterial Wilt of Common Bean, from Turkey
Authors: O’Leary Michael L. , Gilbertson Robert L.
Published: July 2020

Curtobacterium flaccumfaciens pv. flaccumfaciens is the causal agent of bacterial wilt of common bean (Phaseolus vulgaris), a disease that can reduce yields of this economically important crop worldwide. Current genomics resources for this bacterial pathogen are limited. Therefore, long-read sequencing was used to determine the complete genome sequence of a pathogenic C. flaccumfaciens pv. flaccumfaciens strain isolated from common bean leaves showing irregular necrotic lesions with yellow borders collected in a commercial field in Turkey in 2015.
Motorized Internal Lengthening of Long Bones: Residual Limb Lengthening
Authors: Hoellwarth Jason S. , Tetsworth Kevin , Al-Jawazneh Shakib S. , Al Muderis Munjed
Published: July 2020

Distraction osteogenesis can be performed for transfemoral amputees using a motorized intramedullary limb lengthening nail (LLN) such as the 14×130 mm NuVasive Freedom nail. Despite being the shortest commercially available LLN, some patients have even shorter residual femurs, making it impossible to link the bone to the nail by the standard technique of inserting a cross-locking bolt through the proximal and distal nail holes. Two modified techniques of linking a very short femur to a LLN are introduced in this manuscript. The triple cable lasso technique passes 2 cerclage cables transversely through the cortex and then the nail hole, with a third cable clamping the first 2 to the outer cortex. The contoured locking plate technique bends a locking plate to fit over the protruding distal tip of the nail, locks a screw in the plate which threads the distal nail hole, and then locks the plate to the bone with unicortical screws.
Thromboelastography Profiles of Critically Ill Patients With Coronavirus Disease 2019
Authors: Yuriditsky Eugene , Horowitz James M. , Merchan Cristian , Ahuja Tania , Brosnahan Shari B. , McVoy Lauren , Berger Jeffrey S.
Published: July 2020

Objectives:

The rate of thromboembolic events among patients with coronavirus disease 2019 is high; however, there is no robust method to identify those at greatest risk. We reviewed thromboelastography studies in critically ill patients with coronavirus disease 2019 to characterize their coagulation states.

Design:

Retrospective.

Setting:

Tertiary ICU in New York City.

Patients:

Sixty-four patients with coronavirus disease 2019 admitted to the ICU with thromboelastography performed.

Interventions:

None.

Measurements and Main Results:

Fifty percent of patients had a clotting index in the hypercoagulable range (clotting index > 3) (median 3.05). Reaction time and K values were below the lower limit of normal in 43.8% of the population consistent with a hypercoagulable profile. The median α angle and maximum amplitude (75.8° and 72.8 mm, respectively) were in the hypercoagulable range. The α angle was above reference range in 70.3% of patients indicative of rapid clot formation. Maximum amplitude, a factor of fibrinogen and platelet count and function, and a measure of clot strength was above reference range in 60.1% of patients. Thirty-one percent had thromboembolic events; thromboelastography parameters did not correlate with events in our cohort. Those with d-dimer values greater than 2,000 were more likely to have shorter reaction times compared with those with d-dimer levels less than or equal to 2,000 (4.8 vs 5.6 min; p = 0.001).

Conclusions:

A large proportion of critically ill patients with coronavirus disease 2019 have hypercoagulable thromboelastography profiles with additional derangements related to fibrinogen and platelet function. As the majority of patients have an elevated thromboelastography maximum amplitude, a follow-up study evaluating platelet aggregation would be instructive.
Lipofibromatosis-Like Neural Tumor: A Case Report and Review of the Literature
Authors: Crumbach Laura , Descotes Françoise , Bringuier Pierre-Paul , Poulalhon Nicolas , Balme Brigitte , Juliet Tantot , Lopez Jonathan , Harou Olivier
Published: July 2020

Lipofibromatosis-like neural tumors (LPF-NT) are soft tissue tumors characterized by a lipofibromatosis-like pattern, CD34/PS100 positivity, and recurrent NTRK1 gene rearrangement. It occurs mainly in pediatric patients or young adults. We report here, the first case of LPF-NT in a middle-aged adult initially misdiagnosed as a myoepithelial tumor. LPF-NT may have a locally aggressive course but no recurrence was seen after complete surgeries, whereas metastatic diseases remain exceptional.
Sexual function after tension-free vaginal tape procedure in stress urinary incontinence patients
Authors: Zhang Ye , Song Xiaochen , Kang Jia , Ma Yidi , Ma Congcong , Zhu Lan
Published: July 2020

Objective:

The aim of the study was to evaluate sexual function in women before and after tension-free vaginal tape (TVT) surgery for the treatment of stress urinary incontinence (SUI).

Methods:

Between August 2014 and August 2018, 105 sexually active patients with SUI who underwent TVT surgery were enrolled in this prospective cohort study. The Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire Short Form (PISQ-12) was administered pre- and postoperatively. Statistical analyses were performed using paired-sample t tests.

Results:

The sexual function of 105 patients 1 year after the TVT procedure improved in 81 (77.1%) patients, remained unchanged in 18 (17.1%) patients, and deteriorated in 6 (5.7%) patients. The mean PISQ-12 score increased from 29.65 at baseline to 33.04 at the 1-year follow-up (P < 0.001). Improvement was prominent in the physical domain of the PISQ-12 (P < 0.001), but the emotional (P = 0.948) and partner-related (P = 0.915) domains showed no significant changes. The increase in the physical domain score caused the increase of the total PISQ-12 score. Compared with preoperative values, there was no significant change in the score of pain during sexual intercourse (P = 0.425) at 1 year after the TVT procedure. Women experienced less coital incontinence (P < 0.001), less fear of incontinence during intercourse (P < 0.001), and less negative emotional reactions (P < 0.001) during intercourse after the TVT operation than before the TVT operation.

Conclusions:

Sexual function was improved in patients with SUI after TVT surgery.
Basal Cell Carcinoma and Eccrine Porocarcinoma of the Eyelid
Authors: Shoji Marissa K. , Tran Ann Q. , Lazzarini Thomas A. , Choi Catherine J. , Tse Brian C.
Published: July 2020

An 81-year-old woman presented with a progressively enlarging indurated, firm lesion encompassing one-third of the left upper eyelid. Four years prior, a similar lesion at that same site had been excised and diagnosed as a basal cell carcinoma. The patient underwent a full-thickness excision of the lesion with frozen section, cryotherapy, and reconstruction. A free tarsal graft and hard palate composite graft was used to reconstruct the posterior lamella. A Mustarde myocutaneous rotational flap was used to reconstruct the anterior lamella. Histopathology illustrated nests of pleomorphic basophilic cells with varying mitotic activity and immunohistochemical staining consistent with eccrine porocarcinoma. This case highlights similarities in the presentation and appearance of basal cell carcinoma and periorbital eccrine porocarcinoma. It is possible that there was de novo development of the 2 tumors on the eyelid or recurrence of a misdiagnosed eccrine porocarcinoma. Eccrine porocarcinomas are rare malignant sweat gland tumors associated with a risk of recurrence after excision and metastasis.
Supraorbital Neuralgia Associated With Thyroid Eye Disease
Authors: Patrinely J. Randall , Hamilton Kristy L. , Parke Robert B. , Patrinely James R. , Soparkar Charles N. S.
Published: July 2020

Purpose:

To identify the relationship between thyroid eye disease (TED) and supraorbital neuralgia (SON) and establish a reliable approach to the diagnosis and management of TED-associated SON.

Methods:

This retrospective study included 1,126 patients. Demographics, active and inactive phase status and duration, and reactivation rate were noted. TED clinical activity was determined using the vision, inflammation, strabismus, and appearance assessment system, and TED severity was classified using the European Group of Graves’ Orbitopathy system. Subtypes of periorbital pain were identified, and suspected SON was confirmed by supraorbital nerve block.

Results:

Of the study’s 1,126 patients, 935 (83%) were deemed “active” at some point during the follow up and 34 (3%) remained “active” at the study’s conclusion. Of the 2,251 eyes studied, 1,193 (53%) underwent orbital decompression. Of the 1,126 patients, 946 (84%) reported a retrobulbar “pressure” or “aching,” but a distinct, more debilitating pain suggestive of SON was reported in 91 (8%). All 91 patients were given a supraorbital nerve block, and all had complete pain resolution lasting from hours to weeks. Eighty-eight (97%) of the 91 patients with SON-type pain underwent orbital decompression compared to 496 (48%) of the 1,035 without SON-type pain (p < 0.00001). A difference was found in the rate of TED reactivation between those with SON-type symptoms (8%) as compared to those without (2%), p = 0.01.

Conclusions:

SON of uncertain etiology appears to be a previously underreported but significant pain associated with TED. Paradoxically, although the SON does not appear to be related to the type or severity of TED on standard rating scales, the presence of SON was found to be associated with increased likelihood of both orbital decompression and TED reactivation.
Effect of emergency department fibrinogen testing on survival of trauma patients receiving blood transfusions
Authors: White Nathan J. , Chien Diana , Hess John R.
Published: July 2020

Fibrinogen is the first clotting factor to reach critically low levels during blood loss and its depletion is associated with coagulopathy, increased blood loss, transfusion requirements and mortality after trauma. However, direct measurements of fibrinogen concentration or function are not included in many Emergency Department (ED) trauma laboratory testing protocols. We hypothesized that including a test of fibrinogen concentration in the ED would be associated with increased survival for trauma patients requiring blood transfusions.

To test this hypothesis, we performed a single-centre retrospective study of the effect of a resulted fibrinogen concentration measurement performed in the ED on survival of trauma patients receiving blood transfusions within the first 4 h of their hospital arrival. Multivariate logistic regression was used test the effect of a fibrinogen test on hospital survival after adjusting for the influence of INR, injury severity, lowest recorded blood pressure and blood transfusion intensity defined as the number of red blood cell units transfused in the first 4 h or care.

Of 11 404 trauma registry individuals from 2016 to 2017, 843 (7.4%) received any blood transfusions within the first 4 h of ED care, of whom 635 (75.3%) had a documented fibrinogen concentration ordered and resulted. Multivariate logistic regression for hospital survival demonstrated a significant interaction effect between the presence of a fibrinogen test and transfusion intensity (Whole Model P < 0.0001, Interaction P = 0.035). Repeat analysis after stratifying for those individuals receiving more than 4 units of red blood cell units within 4 h of care found that the presence of a fibrinogen test was independently associated with survival only for those receiving more than 4 units [FIB test odds ratio for survival = 3.5 (1.0, 10.8), P = 0.03].

Fibrinogen testing in the ED may be a valuable addition to resuscitation of the trauma patient receiving significant blood transfusions.
Trends in pediatric skin cancer
Authors: Moustafa Danna , Neale Holly , Hawryluk Elena B.
Published: July 2020

Purpose of review

To inform pediatric providers of the clinical characteristics, underlying genetic drivers, and therapeutic options for skin cancer arising in childhood and adolescence.

Recent findings

The incidence of melanoma in pediatric patients has been declining in the past decades. Pediatric-specific diagnostic criteria should be utilized when assessing lesions concerning for melanoma to better account for the different presentations seen in pediatric disease compared with adults, such as an increased prevalence of amelanotic melanoma or frequent mimic of benign pediatric lesions. Pediatric melanoma often presents with a higher histopathologic stage and a higher Breslow depth as compared with adult melanoma. Pediatric nonmelanoma skin cancer including basal cell carcinoma and squamous cell carcinoma are associated with genetic conditions and immunosuppression, both iatrogenic and inherited.

Melanoma in pediatric patients often presents differently from conventional adult melanoma, including Spitz melanoma and melanoma associated with congenital melanocytic nevi. Pediatric patients with nonmelanoma skin cancers should be evaluated for predisposing risk factors. More research on therapeutic options for pediatric skin cancer is vital to understanding the tolerance and response of our pediatric patients to therapies that are more frequently utilized in adult disease.
Pediatric contact dermatitis: what's new
Authors: Tam Idy , Yu JiaDe
Published: July 2020

Purpose of review

Allergic contact dermatitis (ACD) was once thought to be rare in children but recent studies have demonstrated that the prevalence of ACD is common and appears to be increasing in children. Current trends including toys, hobbies, and personal care products may play a role in potentially new allergen exposure or resurgence of certain allergens, making ACD a moving target in children.

Recent findings

ACD and atopic dermatitis can coexist and certain clinical features can help differentiate ACD from endogenous atopic dermatitis in children. It is important to consider ACD in children with recalcitrant atopic dermatitis or dermatitis with atypical distribution. Patch testing has become a more common practice in children. In 2018, the first expert consensus–derived pediatric baseline series consisting of 38 allergens was proposed to aid in the diagnosis of ACD in children. Comparing recent patch testing data in the pediatric population, the top allergens ubiquitously identified were nickel, cobalt, neomycin, Myroxylon pereirae (balsam of Peru), fragrance mix I, fragrance mix II, methylisothiazolinone, methylchloroisothiazolinone/ methylisothiazolinone, formaldehyde, and lanolin.

ACD is a common problem in children. Detection through patch testing, avoidance of offending allergens, and prevention of common allergens are the main focus of management of ACD in children.
Reducing Risks and Improving Vascular Access Outcomes
Authors: Morrell Elizabeth
Published: July 2020

Short peripheral catheter (SPC) insertion is a common invasive procedure performed in hospitalized patients. Variations in this fundamental nursing skill exist among nurses, with significant impacts on budgets, patient satisfaction, and worker safety―key concerns for nurse leaders. A performance improvement project focused on vascular access management was undertaken, with the goal to improve SPC practice and associated outcomes. Assessment of current SPC policies, practices, products, and outcomes identified areas of potential improvement. A performance improvement program was undertaken, and its effects on clinical, safety, and economic outcomes were assessed at 5 hospitals in 1 health care system. Clinical, safety, and economic outcomes improved, as demonstrated by longer average catheter dwell times, increased first-insertion success, improved patient satisfaction, reduced blood exposure, and annual cost savings. A vascular access management program can support leaders in achieving consistent guideline adherent practice among nurses while reducing cost and increasing patient and nurse satisfaction.
Subepidermal Moisture and Pressure Injury in a Pediatric Population
Authors: Bates-Jensen Barbara M. , Reilly Sinead , Hilliard Carol , Patton Declan , Moore Zena
Published: July 2020

PURPOSE

To describe relationships between subepidermal moisture (SEM) and visual skin assessment of pressure injury (PI) in children.

DESIGN:

Prospective descriptive study.

SUBJECTS AND SETTING:

Twenty-four participants aged 8 to 16 years recruited from a pediatric orthopedic unit in a children's hospital in Ireland.

METHODS:

Subepidermal moisture measured with the SEM scanner (Bruin Biometrics, Los Angeles, California) ranged from 0 to 7 picoFarads [pF], and visual observation of trunk and heels occurred daily for 3 days after admission to the unit and/or after surgery. Skin was assessed for discoloration categorized as blanchable erythema, stage 1 PI, or deep tissue injury (DTI). Any open wound PI was classified as stage 2, 3, 4, or unstageable. Demographic, medical, and pain data were collected. Chi-square test, t tests, analysis of variance, and regression were used to describe data and examine relationships.

RESULTS:

Participants were pediatric patients; 100% (n = 24) were white, 62% (n = 15) were female, 8 to 16 years of age (mean = 12.5 ± 2.5 years), and 29% (n = 7) had fractures and 71% (n = 17) surgery diagnoses. Blanchable erythema incidence was 21% (n = 5) and stage 1 PI incidence was 42% (n = 10); nearly all at heels. Deep tissue injury incidence was 4% (one sacral DTI). Stage 2 or greater PI incidence was 4% (one heel stage 2 PI). For skin that was assessed as normal in this pediatric population, SEM for trunk was 2.65 to 2.76 pF and for heels 2.37 to 2.41 pF. Subepidermal moisture for blanchable erythema and stage 1 PI was higher (range, 3.2-3.7 pF) and significant at trochanters and heels (left trochanter: P = .003; right trochanter: P = .02; right and left heels: P = .000). Nominal regression, controlling for participant and assessment day, showed SEM a predictor of erythema and stage 1 PI at heels. We also found that SEM was higher with pain (significant at sacrum and heels).

CONCLUSIONS:

In this pediatric population, SEM values over skin assessed as normal are lower than SEM values reported for normal skin in adults, 2.37 to 2.76 pF. Subepidermal moisture was significantly higher for blanchable erythema and stage 1 PI at trochanters and heels, and with the presence of pain at sacrum and heels. We recommend that SEM should be examined for detecting PIs in pediatric populations; SEM and pain should be explored in larger pediatric and adult populations.
Peristomal Pyoderma Gangrenosum in a Rectal Cancer Patient With an Ileostomy
Authors: Cerdán Santacruz Carlos , Lancharro Bermúdez Margarita , Caparrós Sanz María Rosario , Cerdán Miguel Javier
Published: July 2020

BACKGROUND:

Peristomal pyoderma gangrenosum (PPG) is a rare complication mainly associated with inflammatory bowel disease. Although it has also been found in patients with an ileostomy with rectal cancer, the best treatment options in this context have not been precisely elucidated.

CASE:

This case report describes the importance of a multidisciplinary treatment approach for a rare case of PPG around a protective ileostomy resulting from rectal cancer.

CONCLUSIONS:

Early diagnosis of PPG is imperative to avoid further extension of the lesion. Aggressive management with a multidrug treatment, both topical and systemic, is recommended in severe cases. Close monitoring of the response is necessary, given the variability in the effectiveness of the treatments.
QuoVidi: a open-source web application for the organisation of large scale biological treasure hunts
Authors: Lobet Guillaume , Descamps Charlotte , Leveau Lola , Guillet Alain , Rees Jean-François
Published: July 2020

Learning biology, and in particular systematics, requires learning a substantial amount of specific vocabulary, both for botanical and zoological studies. While crucial, the precise identification of structures serving as evolutionary traits and systematic criteria is not per se a highly motivating task for students. Teaching this in a traditional teaching setting is quite challenging especially with a large crowd of students to be kept engaged. This is even more difficult if, as during the COVID-19 crisis, students are not allowed to access laboratories for hands-on observation on fresh specimens and sometimes restricted to short-range movements outside their home.

Here we present QuoVidi, a new open-source web platform for the organisation of large scale treasure hunts. The platform works as follows: students, organised in teams, receive a list of quests that contain morphologic, ecologic or systematic terms. They have to first understand the meaning of the quests, then go and find them in the environment. Once they find the organism corresponding to a quest, they upload a geotagged picture of their finding and submit this on the platform. The correctness of each submission is evaluated by the staff. During the COVID-19 lockdown, previously validated pictures were also submitted for evaluation to students that were locked in low-biodiversity areas. From a research perspective, the system enables the creation of large image databases by the students, similar to citizen-science projects.

Beside the enhanced motivation of students to learn the vocabulary and perform observations on self-found specimens, this system allows faculties to remotely follow and assess the work performed by large numbers of students. The interface is freely available, open-source and customizable. It can be used in other disciplines with adapted quests and we expect it to be of interest in many classroom settings.
Spatial summation of pain increases logarithmically
Authors: Adamczyk Wacław M. , Manthey Linn , Domeier Christin , Szikszay Tibor M. , Luedtke Kerstin
Published: July 2020

Pain intensity is difficult to predict. Mostly, because of modulatory processes underlying its formation. For example, when nociceptive stimulation occupies a larger body area, pain increases disproportionally. This modulation is called spatial summation of pain (SSp) and is responsible for coding pain intensity. To predict pain based on spatial variables, a profound understanding of the SSp effect is crucial. The aim of this study was i) to describe the SSp effect as a function of the size (or distance) of a stimulated area(s), ii) to investigate the effect of pain intensity on SSp and iii) to evaluate the influence of the SS type on the magnitude of SSp. Thirty-one healthy participants took part in a within-subject experiment. Participants were exposed to area- and distanced based SSp. In the former, electrocutaneous noxious stimuli were applied by up to 5 electrodes (5 areas) forming a line-like pattern at the ulnar side of the hand, while in the latter the same position and lengths of stimuli were used but only two electrodes were stimulated (5 separations). Each paradigm was repeated using pain of low, moderate and high intensity in a random and counterbalanced order. Each stimulus was assessed on a 0-100 scale. It was found that the pattern of increase in pain followed a logarithmic rather than a linear function. The dynamics of the pain increase were statistically different across pain intensities, with more summation occurring, if stimuli were calibrated to eliciting “high” pain. SSp was resistant to saturation in the area-based but not in the distance- based SSp, where 0.8cm separation between two electrodes produced a similar pain intensity as 1.6cm and 2.4cm. Results indicate that area-based SSp is more painful than distance-based SSp when low and moderate but not when high pain intensity is induced. Presented findings have important implications for all studies, in which the spatial dimension of pain is measured. When the area or separation between nociceptive stimulation increases, pain does not increase linearly. Furthermore, the pattern of the pain increase depends on i) intensity and ii) the number of sites of nociception. In conclusion, a logarithmic function should be considered when predicting the size of a nociceptive source. This pattern is indicative for inhibitory processes underlying SSp.
Transcriptomic and morphological response of SIM-A9 mouse microglia to carbon nanotube neuro-sensors
Authors: Yang Darwin , Yang Sarah J. , Del Bonis-O’Donnell Jackson Travis , Pinals Rebecca L. , Landry Markita P.
Published: July 2020

Single-walled carbon nanotubes (SWCNT) are used in neuroscience for deep-brain imaging, neuron activity recording, measuring brain morphology, and imaging neuromodulation. However, the extent to which SWCNT-based probes impact brain tissue is not well understood. Here, we study the impact of (GT)6-SWCNT dopamine nanosensors on SIM-A9 mouse microglial cells and show SWCNT-induced morphological and transcriptomic changes in these brain immune cells. Next, we introduce a strategy to passivate (GT)6-SWCNT nanosensors with PEGylated phospholipids to improve both biocompatibility and dopamine imaging quality. We apply these passivated dopamine nanosensors to image electrically stimulated striatal dopamine release in acute mouse brain slices, and show that slices labeled with passivated nanosensor exhibit higher fluorescence response to dopamine and measure more putative dopamine release sites. Hence, this facile modification to SWCNT-based dopamine probes provides immediate improvements to both biocompatibility and dopamine imaging functionality with an approach that is readily translatable to other SWCNT-based neurotechnologies.
Theory-guided development of fertility care implementation strategies for adolescents and young adult cancer survivors
Authors: Dornish Anna , Yang Emily M. , Gruspe Jamie , Roesch Erin R. , Aristizabal Paula , Aarons Greg A. , Romero Sally A.D. , Takemoto Michelle B. , Kaiser Bonnie N. , Su H. Irene
Published: July 2020

Background

Oncofertility care remains under-implemented across oncology and fertility care settings, with limited tools to scale up effective implementation strategies. Guided by the Consolidated Framework for Implementation Research (CFIR), we aimed to systematically assess factors that influence implementation of oncofertility care and map strategies, particularly electronic health record (EHR)-enabled ones, that fit adult and pediatric oncology care contexts.

Methods

Using purposeful sampling, we recruited healthcare providers and female adolescent and young adult (AYA) cancer survivors from a comprehensive cancer center and a freestanding children’s hospital. Participants underwent semi-structured interviews and focus groups. Using thematic analysis combining inductive codes with CFIR-based deductive codes, we characterized barriers and facilitators to oncofertility care and implementation strategies. Two coders independently coded each transcript, with a third coder resolving discrepancies by consensus.

Results

We recruited 19 oncology and fertility providers and 9 AYA survivors. We identified barriers and facilitators to fertility care in the CFIR domains of individual, inner setting, outer setting, and process, allowing us to conceptualize oncofertility care in three necessary stages: screening, referral, and fertility preservation counseling. To fit an adult and a children’s context, five implementation strategies were mapped: needs screen using a best practice advisory, referral order, telehealth fertility counseling, provider audit and feedback, and a provider educational session. All but provider education are facilitated by the EHR system.

Conclusions

An implementation science approach enabled systematic assessment of oncofertility care and co-design of implementation strategies with stakeholders, providing a theory-based approach and scalable EHR tools to support wider dissemination.
Identification of peptide candidate against COVID-19 through reverse vaccinology: An immunoinformatics approach
Authors: Das Rohit Pritam , Jagadeb Manaswini , Rath Surya Narayan
Published: July 2020

Novel corona virus disease 2019 (COVID-19) is emerging as a pandemic situation and declared as a global health emergency by WHO. Due to lack of specific medicine and vaccine, viral infection has gained a frightening rate and created a devastating state across the globe. Here authors have attempted to design epitope based potential peptide as a vaccine candidate using immunoinformatics approach. As of evidence from literatures, SARS-CoV-2 Spike protein is a key protein to initiate the viral infection within a host cell thus used here as a reasonable vaccine target. We have predicted a 9-mer peptide as representative of both B-cell and T-cell epitopic region along with suitable properties such as antigenic and non-allergenic. To its support, strong molecular interaction of the predicted peptide was also observed with MHC molecules and Toll Like receptors. The present study may helpful to step forward in the development of vaccine candidates against COVID-19.
High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity
Authors: Lu Jinghua , Sun Peter D.
Published: July 2020

A novel coronavirus (SARS-CoV-2) has emerged to a global pandemic and caused significant damages to public health. Human angiotensin-converting enzyme 2(ACE2) was identified as the entry receptor for SARS-CoV-2. As a carboxypeptidase, ACE2 cleaves many biological substrates besides Ang II to control vasodilatation and permeability. Given the nanomolar high affinity between ACE2 and SARS-CoV-2 spike protein, we wonder how this interaction would affect the enzymatic activity of ACE2. Surprisingly, SARS-CoV-2 trimeric spike protein increased ACE2 proteolytic activity ~3-10 fold when fluorogenic caspase-1 substrate and Bradykinin-analog peptides were used to characterize ACE2 activity. In addition, the enhancement was mediated by ACE2 binding of RBD domain of SARS-CoV-2 spike. These results highlighted the altered activity of ACE2 during SARS-CoV-2 infection and would shed new lights on the pathogenesis of COVID-19 and its complications for better treatments.
The UPRmtPreserves Mitochondrial Import to Extend Lifespan
Authors: Xin Nan , Durieux Jenni , Yang Chunxia , Wolff Suzanne , Kim Hyun-Eui , Dillin Andrew
Published: July 2020

The mitochondrial unfolded protein response (UPRmt) is dedicated to promote mitochondrial proteostasis and is linked to extreme longevity in worms, flies, and mice. The key regulator of this process is the transcription factor, ATFS-1. In the absence of mitochondrial stress, ATFS-1 is transported to the mitochondria and degraded. During conditions of mitochondrial stress, ATFS-1 is excluded from the mitochondria and enters the nucleus to regulate the expression of UPRmtgenes. However, there exists a dichotomy in regards to induction of the UPRmtand mitochondrial import. The repair proteins synthesized as a direct result of UPRmtactivation must be transported into damaged mitochondria that had previously excluded ATFS-1 due to reduced import efficiency. To address this conundrum, we analyzed the role of the import machinery under conditions where the UPRmtwas induced. Usingin vitrobiochemical assays of mitochondrial import andin vivoanalysis of mitochondrial proteins, we surprisingly find that the efficiency of mitochondrial import increases when the UPRmtis activated in an ATFS-1 dependent manner, even though membrane potential is reduced. The import machinery is upregulated at the transcription and translation level, and intact import machinery is essential for UPRmt-mediated increase and lifespan extension. With age, import capacity decreases, and activation of the UPRmtdelays this decline and increases longevity. Finally, we find that ATFS-1 has a significantly weaker mitochondrial targeting sequence (MTS), allowing for dynamic subcellular localization during the initial stages of UPRmtactivation.
A simple and highly efficient method for multi-allelic CRISPR-Cas9 editing in primary cell cultures
Authors: Hoellerbauer Pia , Kufeld Megan , Arora Sonali , Wu Hua-Jun , Feldman Heather M. , Paddison Patrick J.
Published: July 2020

Background

CRISPR-Cas9-based technologies have revolutionized experimental manipulation of mammalian genomes. None-the-less, limitations of the delivery and efficacy of these technologies restrict their application in primary cells.

Aims

To create an optimized protocol for penetrant, reproducible, and fast targeted insertiondeletion mutation (indel) formation in cell cultures derived from primary cells, using patient-derived glioblastoma (GBM) stem-like cells (GSCs) and human neural stem/progenitor cells (NSCs) for proof-of-concept experiments.

Methods

We employed transient nucleofection of Cas9:sgRNA ribonucleoprotein complexes using chemically synthesized 2’-O-methyl 3’phosphorothioate-modified sgRNAs and purified Cas9 protein. Indel frequency and size distribution were measured via computational deconvolution of Sanger sequencing trace data. Western blotting was used to evaluate protein loss. RNA-seq in edited NSCs was used to assess gene expression changes resulting from knockout of tumor suppressors commonly altered in GBM.

Results

We found that with this optimized technique, we can routinely achieve >90% indel formation in only 3 days, without the need to create clonal lines for simple loss-of-function experiments. We observed near-total protein loss of target genes in cell pools. Additionally, we found that this approach allows for the creation of targeted genomic deletions. We also demonstrated the utility of this method for quickly creating a series of gene knockouts that allow for the study of oncogenic activities.

Conclusion

Our data suggest that this relatively simple method can be used for highly efficient and fast gene knockout, as well as for targeted genomic deletions, even in hyperdiploid cells (such as GSCs). This represents an extremely useful tool for the cancer research community when wishing to inactivate not only coding genes, but also non-coding RNAs, UTRs, enhancers, and promoters. This method can be readily applied to diverse cell types by varying the nucleofection conditions.
Broad phenotypic alterations and potential dysfunctions of lymphocytes in COVID-19 recovered individuals
Authors: Yang Jingyi , Zhong Maohua , Zhang Ejuan , Hong Ke , Yang Qingyu , Zhou Dihan , Xia Jianbo , Chen Yao-Qing , Sun Mingbo , Zhao Bali , Xiang Jie , Liu Ying , Han Yang , Zhou Xi , Huang Chaolin , Shang You , Yan Huimin
Published: July 2020

Background

Lymphopenia is a typical symptom in the COVID-19 patients. While millions of patients are clinical recovered, little is known about the immune status of lymphocytes in these individuals.

Methods

A clinical recovered cohort (CR) of 55 COVID-19 individuals (discharged from hospital 4 to 11 weeks), and 55 age and sex matched healthy donors cohort (HD) were recruited. Detailed analysis on phenotype of the lymphocytes in peripheral blood mononuclear cells (PBMCs) was performed by flow cytometry.

Findings

Compared with cohort HD, the CD8+T cells in cohort CR had higher Teff and Tem, but lower Tc1 (IFN-γ+), Tc2 (IL-4+) and Tc17 (IL-17A+) frequencies. The CD4+T cells of CR had decreased frequency, especially on the Tcm subset. Moreover, CD4+T cells of CR expressed lower PD-1 and had lower frequencies of Th1 (IFN-γ+), Th2 (IL-4+), Th17 (IL-17A+) as well as circulating Tfh (CXCR5+PD-1+). Accordingly, isotype-switched memory B cell (IgM-CD20hi) in CR had significantly lower proportion in B cells, though level of activation marker CD71 elevated. For CD3-HLA-DRlolymphocytes of CR, besides levels of IFN-γ, Granzyme B and T-bet were lower, the correlation between T-bet and IFN-γ became irrelevant. In addition, taken into account of discharged days, all the lowered function associated phenotypes showed no recovery tendency within whole observation period.

Interpretation

The CR COVID-19 individuals still showed remarkable phenotypic alterations in lymphocytes after clinical recovery 4 to 11 weeks. This suggests SARS-CoV-2 infection imprints profoundly on lymphocytes and results in long-lasting potential dysfunctions.

Funding

Kunming Science and Technology Department (2020-1-N-037)
Temporary Immunity and Multiple Waves of COVID-19
Authors: Shayak B , Sharma Mohit M , Misra Anoop
Published: July 2020

In this work we use mathematical modeling to describe the potential phenomena which may occur if immunity to COVID-19 lasts for a finite time instead of being permanent, i.e. if a recovered COVID-19 patient may again become susceptible to the virus after a given time interval following his/her recovery. Whether this really happens or not is unknown at the current time. If it does happen, then we find that for certain combinations of parameter values (social mobility, contact tracing, immunity threshold duration etc), the disease can keep recurring in wave after wave of outbreaks, with a periodicity approximately equal to twice the immunity threshold. Such cyclical attacks can be prevented trivially if public health interventions are strong enough to contain the disease outright. Of greater interest is the finding that should such effective interventions not prove possible, then also the second and subsequent waves can be forestalled by a consciously relaxed intervention level which finishes off the first wave before the immunity threshold is breached. Such an approach leads to higher case counts in the immediate term but significantly lower counts in the long term as well as a drastically shortened overall course of the epidemic.

As we write this, there are more than 1,00,00,000 cases (at least, detected cases) and more than 5,00,000 deaths due to COVID-19 all over the globe. The unknowns surrounding this disease outnumber the knowns by orders of magnitude. One of these unknowns is how long does immunity last i.e., once a person recovers from COVID-19 infection, how long does s/he remain insusceptible to a fresh infection. Most modeling studies assume lifetime immunity, or at least sufficiently prolonged immunity as to last until the outbreak is completely over. Among the exceptions are Giordano et. al. [1] and Bjornstad et. al. [2] who account for the possibility of re-infection – while the former find no special behaviour on account of this, the latter find an oscillatory approach towards the eventual equilibrium. In an article which appeared today, Kosinski [3] has found multiple waves of COVID-19 if the immunity threshold is finite. The question of whether COVID-19 re-infection can occur is completely open as of now. A study [4] has found that for benign coronaviruses (NOT the COVID-19 pathogen!), antibodies become significantly weaker six months after the original infection, and re-infection is common from one year onwards. Although it is currently unknown whether COVID-19 re-infections can occur, the mere possibility is sufficiently frightening as to warrant a discussion of what might happen if it is true. In this Article, we use mathematical modeling to present such a discussion. Before starting off, let us declare in the clearest possible terms that this entire Article is a what-if analysis, predicated on an assumption whose veracity is not known at the current time. The contents of this Article are therefore hypothetical – as of now they are neither factual nor counter-factual.
The impact of contact tracing and household bubbles on deconfinement strategies for COVID-19: an individual-based modelling study
Authors: Willem Lander , Abrams Steven , Petrof Oana , Coletti Pietro , Kuylen Elise , Libin Pieter , Møgelmose Signe , Wambua James , Herzog Sereina A. , Faes Christel ,   SIMID COVID19 team, Beutels Philippe , Hens Niel
Published: July 2020

Background

The rising COVID-19 pandemic caused many governments to impose policies restricting social interactions. These policies have slowed down the spread of the SARS-CoV-2 virus to the extent that restrictions can be gradually lifted. Models can be useful to assess the consequences of deconfinement strategies with respect to business, school and leisure activities.

Methods

We adapted the individual-based model “STRIDE” to simulate interactions between the 11 million inhabitants of Belgium at the levels of households, workplaces, schools and communities. We calibrated our model to observed hospital incidence and seroprevalence data. STRIDE can explore contact tracing options and account for repetitive leisure contacts in extended household settings (so called “household bubbles”) with varying levels of connectivity.

Findings

Household bubbles have the potential to reduce the number of COVID-19 hospital admissions by up to 90%. The effectiveness of contact tracing depends on its timing, as it becomes futile more than 4 days after the index case developed symptoms. Assuming that children have a lower level of susceptibility and lower probability to experience symptomatic SARS-CoV-2 infection, (partial) school closure options have relatively little impact on COVID-19 burden.

Interpretation

Not only the absolute number and intensity of physical contacts drive the transmission dynamics and COVID-19 burden, also their repetitiveness is influential. Contact tracing seems essential for a controlled and persistent release of lockdown measures, but requires timely compliance to testing, reporting and self-isolation. Rapid tracing and testing, and communication ensuring continued involvement of the population are therefore essential.
Corporate governance practices and capital structure decisions: the moderating effect of gender diversity
Authors: A.A Zaid Mohammad , Wang Man , T.F. Abuhijleh Sara , Issa Ayman , W.A. Saleh Mohammed , Ali Farman
Published: July 2020

Purpose

Motivated by the agency theory, this study aims to empirically examine the nexus between board attributes and a firm’s financing decisions of non-financial listed firms in Palestine and how the previous relationship is moderated and shaped by the level of gender diversity.

Design/methodology/approach

Multiple regression analysis on a panel data was used. Further, we applied three different approaches of static panel data “pooled OLS, fixed effect and random effect.” Fixed-effects estimator was selected as the optimal and most appropriate model. In addition, to control for the potential endogeneity problem and to profoundly analyze the study data, the authors perform the one-step system generalized method of moments (GMM) estimator. Dynamic panel GMM specification was superior in generating robust findings.

Findings

The findings clearly unveil that all explanatory variables in the study model have a significant influence on the firm’s financing decisions. Moreover, the results report that the impact of board size and board independence are more positive under conditions of a high level of gender diversity, whereas the influence of CEO duality on the firm’s leverage level turned from negative to positive. In a nutshell, gender diversity moderates the effect of board structure on a firm’s financing decisions.

Research limitations/implications

This study was restricted to one institutional context (Palestine); therefore, the results reflect the attributes of the Palestinian business environment. In this vein, it is possible to generate different findings in other countries, particularly in developed markets.

Practical implications

The findings of this study can draw responsible parties and policymakers’ attention in developing countries to introduce and contextualize new mechanisms that can lead to better monitoring process and help firms in attracting better resources and establishing an optimal capital structure. For instance, entities should mandate a minimum quota for the proportion of women incorporation in boardrooms.

Originality/value

This study provides empirical evidence on the moderating role of gender diversity on the effect of board structure on firm’s financing decisions, something that was predominantly neglected by the earlier studies and has not yet examined by ancestors. Thereby, to protrude nuanced understanding of this novel and unprecedented idea, this study thoroughly bridges this research gap and contributes practically and theoretically to the existing corporate governance–capital structure literature.