bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the 13-valent pneumococcal conjugate vaccine on acute otitis media and acute sinusitis epidemiology in British Columbia, Canada
Authors: Vadlamudi Nirma Khatri , Saatchi Ariana , Patrick David M. , Rose Caren , Sadatsafavi Mohsen , Marra Fawziah
Published: April 2021

Background

Numerous studies have characterized the 13-valent pneumococcal conjugate vaccine (PCV13) programme’s beneficial effects on acute otitis media (AOM) and acute sinusitis (AS) rates in children; however, few studies have examined the impact on adults.

Objectives

This retrospective cohort study evaluates the overall effect of the PCV13 immunization programme on the incidence of AOM and AS at the population level.

Methods

Health administrative databases were linked to assess outpatient visits, hospitalizations and antibiotic utilization from 2000 to 2018. Multivariable Poisson regression was used to evaluate the impact of the PCV13 vaccine programme (2011–18) compared with the pre-PCV13 era (2000–10), overall and by age.

Results

From 2000 to 2018, the incidence of AOM decreased by 50% (62 to 31 per 1000 population) while sinusitis decreased by 18% (33 to 27 per 1000 population). In the PCV13 era, the incidence of AOM declined [incidence rate ratio (IRR): 0.70; 95% CI: 0.70–0.70], in parallel with decreased incidence of antibiotic utilization (IRR: 0.65; 95% CI: 0.64–0.65). A reduction was also observed in the incidence of AS during the PCV13 era compared with the pre-PCV13 era (IRR: 0.88; 95% CI: 0.88–0.88), mainly driven by declines among those younger than 65 years of age. In contrast, an increase in AS incidence was noted in individuals aged ≥65 years (IRR: 1.03; 95% CI: 1.02–1.03). A decrease in antibiotic prescription rates for sinusitis was observed for those under 65 years of age.

Conclusions

The PCV13 immunization programme is associated with a reduction in the incidence of AOM and AS. Moreover, the associated use of antibiotics for these diagnoses has comparably decreased across paediatric, as well as adult populations.
Development of a liquid chromatography–electrospray ionization tandem mass spectrometric method for the simultaneous analysis of free fatty acids
Authors: Lee-Okada Hyeon-Cheol , Hama Kotaro , Yokoyama Kazuaki , Yokomizo Takehiko
Published: April 2021

Fatty acids (FAs) play important roles in several physiological and pathophysiological processes, functioning as both nonesterified free FAs (FFAs) and components of other lipid classes. Although many lipid classes are readily measured using liquid chromatography–electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS), the measurement of FFAs by this method is not straightforward because of inconsistent fragmentation behaviours. In this study, we describe a strategy to measure FFAs using conventional reverse-phase LC-ESI-MS/MS, without derivatization. The strategy combines three key methods: (i) an isocratic LC separation with a high organic solvent ratio, (ii) postcolumn base addition, and (iii) pseudo-multiple reaction monitoring. The method facilitates the measurement of ultra-long-chain FAs, the accumulation of which is a common biochemical abnormality in peroxisomal disorders. This study delivers a broad strategy that measures a wide spectrum of FFA species in complex biological samples.
Female Southern White Rhinoceros Can Select Mates to Avoid Inbreeding
Authors: Stratford Ken J , Guerier Abigail S , Crawford Stuart J , Stratford Sabina M C , Schmidt-Küntzel Anne , Bishop Jacqueline M
Published: April 2021

Current management models for many endangered species focus primarily on demographic recovery, often ignoring their intrinsic ecological requirements. Across the protected area network of southern Africa, most southern white rhinoceros are managed in populations of less than 50 individuals, experiencing restricted dispersal opportunities, and limited breeding male numbers due to their exclusive home range requirements. In the absence of information on the breeding structure of these populations, poor management decisions may require females to either forego a breeding opportunity or select to inbreed with close relatives. Here, we use a combination of social pedigree data together with genetic analyses to reconstruct the parentage of all 28 offspring produced in a 5-year period in a managed free-ranging southern white rhinoceros population. During this period, all breeding females (founders and first-generation daughters) had access to both a founder male (father to most of the daughters) and two recently introduced inexperienced males. We report that while founder females were more likely to breed with the founder male, their daughters, in contrast, were more likely to breed with the introduced males, thus avoiding inbreeding. However, we also found evidence of father–daughter inbreeding in this population, and contend that in the absence of choice, rather than forego a breeding opportunity, female white rhinoceros will inbreed with their fathers. We argue that to effectively conserve the southern white rhinoceros, managers need to understand the breeding structure of these small populations, particularly in terms of parentage and kinship.
Potential Hurricane Wind Risk to US Rural and Urban Forests
Authors: Cole Jason , Nowak David J , Greenfield Eric J
Published: April 2021

Hurricanes cause billions of dollars in damage annually in the United States and are projected to increase in intensity in the coming years. By exploring historical patterns of hurricanes and exposure of these hurricane-force winds across the landscape, areas of potentially high threat to future hurricane winds can be revealed. Combining potential threats from hurricane winds with forest data reveal the areas with the greatest potential threats to this important resource. Not surprisingly, most of the threats to forests occur in the Southeast, but the greatest threats to urban forests overall occur along the Northeast coast and in metropolitan centers in the Southeast. Overall, 4.6% of the nation’s rural forest basal area is within zones of the highest risk from hurricane winds. Information on regional and local scale variations in hurricane risk can be used to aid policies and local forest management to improve forest health and sustainability.
Prospective Evaluation of Galactomannan and (1→3) β-d-Glucan Assays as Diagnostic Tools for Invasive Fungal Disease in Children, Adolescents, and Young Adults With Acute Myeloid Leukemia Receiving Fungal Prophylaxis
Authors: Fisher Brian T , Westling Ted , Boge Craig L K , Zaoutis Theoklis E , Dvorak Christopher C , Nieder Michael , Zerr Danielle M , Wingard John R , Villaluna Doojduen , Esbenshade Adam J , Alexander Sarah , Gunn Suphansa , Wheat Lawrence J , Sung Lillian
Published: April 2021

Background

Patients receiving chemotherapy for acute myeloid leukemia (AML) are at high risk for invasive fungal disease (IFD). Diagnosis of IFD is challenging, leading to interest in fungal biomarkers. The objective was to define the utility of surveillance testing with Platelia Aspergillus galactomannan (GM) enzyme immunoassay (EIA) and Fungitell β-d-glucan (BDG) assay in children with AML receiving antifungal prophylaxis.

Methods

Twice-weekly surveillance blood testing with GM EIA and BDG assay was performed during periods of neutropenia in the context of a randomized trial of children, adolescents, and young adults with AML allocated to fluconazole or caspofungin prophylaxis. Proven or probable IFD was adjudicated using blinded central reviewers. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for Platelia and Fungitell assays alone and in combination for the outcomes of proven and probable invasive aspergillosis (IA) or invasive candidiasis (IC).

Results

Among 471 patients enrolled, 425 participants (209 fluconazole and 216 caspofungin) contributed ≥1 blood specimen. In total, 6103 specimens were evaluated, with a median of 15 specimens per patient (range 1–43). The NPV was >99% for GM EIA and BDG assay alone and in combination. However, there were no true positive results, resulting in sensitivity and PPV for each assay of 0%.

Conclusions

The GM EIA and the BDG assay alone or in combination were not successful at detecting IA or IC during periods of neutropenia in children, adolescents, and young adults with AML receiving antifungal prophylaxis. Utilization of these assays for surveillance in this clinical setting should be discouraged.
Synthesis of 3,3-dimethyl-6-oxopyrano[3,4-c]pyridines and their antiplatelet and vasodilatory activity
Authors: Sirakanyan Samvel N , Hrubša Marcel , Spinelli Domenico , Dias Patrícia , Kartsev Victor , Carazo Alejandro , Hovakimyan Anush A , Pourová Jana , Hakobyan Elmira K , Karlíčková Jana , Parvin Shamima , Fadraersada Jaka , Macáková Kateřina , Geronikaki Athina , Mladěnka Přemysl
Published: April 2021

Objectives

Both pyridine and pyrano derivatives have been previously shown to possess biologically relevant activity. In this study, we report the incorporation of these two scaffolds into one molecule.

Methods

The designed 3,3-dimethyl-6-oxopyrano[3,4-c]pyridines were synthesized by the acylation of enamine under Stork conditions followed by condensation of formed β-diketones with 2-cyanoacetamide. The structures of these compounds were confirmed by using a wide spectrum of physico-chemical methods. Their antiplatelet, anticoagulant and vasodilatory activity together with toxicity were evaluated.

Key findings

A series of 6-oxopyrano[3,4-c]pyridines 3a–j was obtained. Four of these compounds were reported for the first time. None of the tested compounds demonstrated anticoagulant effect but 8-methyl derivative (3a) was a potent antiplatelet compound with IC50 numerically twice as low as the clinically used acetylsalicylic acid. A series of further mechanistic tests showed that 3a interferes with calcium signaling. The compound is also not toxic and in addition possesses vasodilatory activity as well.

Conclusions

Compound 3a is a promising inhibitor of platelet aggregation, whose mechanism of action should be studied in detail.
Right hemicolectomy for ileocolonic intussusception in an adult with active COVID-19 infection: a case report
Authors: Jackson Katherine M , Sabbota Aaron L
Published: April 2021

The most common symptoms of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are fevers, fatigue and dry cough. However, growing data suggest gastrointestinal (GI) manifestations occur in the majority of patients. Small bowel obstruction remains a significant cause of surgical abdominal emergencies in the adult population, although most cases are secondary to adhesive disease. We present a case of ileocolonic intussusception in an adult with active COVID-19 infection. Our patient presented with small bowel obstruction 4 days after diagnosis of COVID-19 with typical respiratory symptoms. Imaging revealed ileocolonic intussusception and possible cecal mass for which a right hemicolectomy was performed. Recovery was unremarkable. Pathology suggested necrosis without an identifiable mass. To the best of our knowledge, this is the first documented case of small bowel obstruction secondary to ileocolonic intussusception in an adult related to GI manifestation of COVID-19.
Duodenal recurrence of endometrial carcinoma: report of a rare metastatic site
Authors: Pinheiro João L , Marques Marisa , Daniel Carlos , Pereira Jorge , Casimiro Carlos
Published: April 2021

Endometrial carcinoma is one of the most common gynaecologic malignancies in the western society. Treatment of recurrent disease became more refined, with the study of molecular and hormonal receptors playing a central role. A 76-year-old caucasian woman presented to the emergency department with growing tiredness, and melaena. Past medical history included an endometrioid adenocarcinoma. The patient had undergone a hysterectomy with bilateral salpingo-oophorectomy with pelvic and paraaortic lymphadenectomy and was disease-free for 2 years. The endoscopy revealed an ulcerated lesion involving the second and third portions of the duodenum. Histopathologic examination confirmed a poorly differentiated adenocarcinoma of endometrial origin. She started palliative chemotherapy, remaining with adequate symptomatic control. Endometrial cancer recurrence typically occurs locally. The liver is the intra-abdominal organ most commonly involved. There are scarce reports of duodenal metastasis of malignancies originated in distant organs. The duodenum remains an uncommon metastization site and is rarely associated with endometrial cancer.
Use of a Digital Cognitive Aid Improves Memorization of Military Caregivers After High-Fidelity Simulations of Combat Casualty Care
Authors: Paraschiv Andrei-Petru , Balança Baptiste , Lilot Marc , Aigle Luc , Lehot Jean-Jacques , Cejka Jean-Christophe
Published: April 2021

Introduction

High-fidelity simulation is widely used in the ongoing education of caregivers. However, the complex high-stakes simulated crisis environment affects memorization. This study investigated whether participants would remember more key training messages 3 months after a simulated complex emergency situation if they had used a digital cognitive aid (CA) during the simulations.

Materials and Methods

This randomized controlled trial was performed during a combat casualty training course for military physicians and nurses. Each pair of care providers completed two scenarios randomized to be undertaken either with or without a digital CA. At the end of each debriefing, instructors gave five scenario-specific key messages aloud. Three months later, learners were asked to recall the messages from their two scenarios and were scored for each scenario. The primary endpoint was the number of key messages recalled. The secondary endpoints were the influence on the results of the profession and the scenario block and age of the leader.

Results

Thirty-six pairs of participants were included. Due to operational constraints, only 34 completed the study. The use of the digital CA was associated with a positive effect on memorization at 3 months (F = 82.2, P < .001), unrelated to the leader’s profession, age, or the scenario block. The median of the memorization scores was 2/5 [1-3] with the digital CA and 1/5 [1-1] without it, which represents a difference of one memorized element (95% CI, 1-2; η2 = 0.39).

Conclusions

The digital CA allowed learners to remember twice as many key elements 3 months after simulated training of medical care for military combat casualties. A dedicated digital CA might be an asset for better care in a combat environment and for learning and memorizing critical care procedures following complex emergency situations.
Deep generative models for galaxy image simulations
Authors: Lanusse François , Mandelbaum Rachel , Ravanbakhsh Siamak , Li Chun-Liang , Freeman Peter , Póczos Barnabás
Published: April 2021

Image simulations are essential tools for preparing and validating the analysis of current and future wide-field optical surveys. However, the galaxy models used as the basis for these simulations are typically limited to simple parametric light profiles, or use a fairly limited amount of available space-based data. In this work, we propose a methodology based on deep generative models to create complex models of galaxy morphologies that may meet the image simulation needs of upcoming surveys. We address the technical challenges associated with learning this morphology model from noisy and point spread function (PSF)-convolved images by building a hybrid Deep Learning/physical Bayesian hierarchical model for observed images, explicitly accounting for the PSF and noise properties. The generative model is further made conditional on physical galaxy parameters, to allow for sampling new light profiles from specific galaxy populations. We demonstrate our ability to train and sample from such a model on galaxy postage stamps from the HST/ACS COSMOS survey, and validate the quality of the model using a range of second- and higher order morphology statistics. Using this set of statistics, we demonstrate significantly more realistic morphologies using these deep generative models compared to conventional parametric models. To help make these generative models practical tools for the community, we introduce galsim-hub, a community-driven repository of generative models, and a framework for incorporating generative models within the galsim image simulation software.
Revisiting the structure function of PSR B0950+08 scintillations
Authors: Goldman Itzhak
Published: April 2021

The observational structure function of the scintillations of the radio pulsar PSR B0950+08 was fitted, a decade ago, with a power law with index 1 ± 0.05. This was interpreted as an appreciable deviation from the commonly observed index of 5/3, expected for Kolmogorov turbulence. In this paper, it is suggested that the observations are consistent with a Kolmogorov turbulence and that the apparent deviation is due to a turbulent region with an effective depth, which is comparable to the observed lateral scales on the plane of the sky, spanned by the pulsar beam. Alternatively, the fitted index of 1 is consistent with an underlying compressive turbulence and an even smaller depth. In the first interpretation, the depth is (5.5 ± 1.8) × 108 cm. In the second one, the depth is ≲4 × 107 cm. These estimates lend support for the existence of extremely thin, ionized scattering screens in the local interstellar cloud that have been proposed a decade ago.
Precise diffusion coefficients for white dwarf astrophysics
Authors: Caplan M E , Freeman I F
Published: April 2021

Observations of Galactic white dwarfs with Gaia have allowed for unprecedented modelling of white dwarf cooling, resolving core crystallization, and sedimentary heating from neutron-rich nuclei. These cooling sequences are sensitive to the diffusion coefficients of nuclei in Coulomb plasmas which have order 10 per cent uncertainty and are often not valid across coupling regimes. Using large-scale molecular dynamics simulations we calculate diffusion coefficients at high resolution in the regime relevant for white dwarf modelling. We present a physically motivated law for diffusion with a semi-empirical correction which is accurate at the percent level. Implemented along with linear mixing in stellar evolution codes, this law should reduce the error from diffusion coefficients by an order of magnitude.
Evaluation of a Commercial Culture-Free Neutralization Antibody Detection Kit for Severe Acute Respiratory Syndrome-Related Coronavirus-2 and Comparison With an Antireceptor-Binding Domain Enzyme-Linked Immunosorbent Assay
Authors: Papenburg Jesse , Cheng Matthew P , Corsini Rachel , Caya Chelsea , Mendoza Emelissa , Manguiat Kathy , Lindsay L Robbin , Wood Heidi , Drebot Michael A , Dibernardo Antonia , Zaharatos Gerasimos , Bazin Reneé , Gasser Romain , Benlarbi Mehdi , Gendron-Lepage Gabrielle , Beaudoin-Bussières Guillaume , Prévost Jérémie , Finzi Andrés , Ndao Momar , Yansouni Cedric P
Published: April 2021

Background

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) surrogate neutralization assays that obviate the need for viral culture offer substantial advantages regarding throughput and cost. The cPass SARS-CoV-2 Neutralization Antibody Detection Kit (GenScript) is the first such commercially available assay that detects antibodies that block receptor-binding domain (RBD)/angiotensin-converting enzyme (ACE)-2 interaction. We aimed to evaluate cPass to inform its use and assess its added value compared with anti-RBD enzyme-linked immunosorbent assays (ELISAs).

Methods

Serum reference panels comprising 205 specimens were used to compare cPass to plaque-reduction neutralization test (PRNT) and a pseudotyped lentiviral neutralization (PLV) assay for detection of neutralizing antibodies. We assessed the correlation of cPass with an ELISA detecting anti-RBD immunoglobulin (Ig)G, IgM, and IgA antibodies at a single timepoint and across intervals from onset of symptoms of SARS-CoV-2 infection.

Results

Compared with PRNT-50, cPass sensitivity ranged from 77% to 100% and specificity was 95% to 100%. Sensitivity was also high compared with the pseudotyped lentiviral neutralization assay (93%; 95% confidence interval [CI], 85–97), but specificity was lower (58%; 95% CI, 48–67). Highest agreement between cPass and ELISA was for anti-RBD IgG (r = 0.823). Against the pseudotyped lentiviral neutralization assay, anti-RBD IgG sensitivity (99%; 95% CI, 94–100) was very similar to that of cPass, but overall specificity was lower (37%; 95% CI, 28–47). Against PRNT-50, results of cPass and anti-RBD IgG were nearly identical.

Conclusions

The added value of cPass compared with an IgG anti-RBD ELISA was modest.
Thrombectomy and Clip Occlusion of a Giant, Stent-Coiled Basilar Bifurcation Aneurysm: 3-Dimensional Operative Video
Authors: Frisoli Fabio A , Catapano Joshua S , Farber S Harrison , Baranoski Jacob F , Singh Rohin , Benet Arnau , Cole Tyler S , Mooney Michael A , Srinivasan Visish M , Lawton Michael T
Published: April 2021

Giant basilar apex aneurysms are associated with significant therapeutic challenges.
1–6
Multiple techniques exist to treat giant basilar apex aneurysms, including direct clipping, stent-assisted coil embolization, and proximal occlusion with bypass revascularization.
7–9
Hypothermic circulatory arrest was a useful adjunct for surgical repair of these aneurysms but has been abandoned because of associated risks.
10,11
Rapid ventricular pacing can achieve similar aneurysm softening with minimal risks and assist in clip occlusion. This case illustrates clip occlusion of a giant, partially thrombosed, previously stent-coiled basilar apex aneurysm in a 15-yr-old boy with progressive cranial neuropathies and sensorimotor impairment. Although a wire was placed preoperatively for ventricular pacing, it was not needed during the procedure. Patient consent was obtained. A right-sided orbitozygomatic craniotomy transcavernous approach with anterior and posterior clinoidectomies was performed. The basilar quadrification was dissected, and proximal control was obtained. After aneurysm trapping, the aneurysm was incised and thrombectomized using an ultrasonic aspirator. Back-bleeding from the aneurysm was anticipated, and ventricular pacing was ready, but back-bleeding was minimal. With the coil mass left in place, stacked, fenestrated clips were applied in a tandem fashion to occlude the aneurysm neck. Indocyanine green videoangiography confirmed occlusion of the aneurysm and patency of parent and branch arteries. The patient was at a neurological baseline after the operation, with improvement in motor skills and cognition at 3-mo follow-up. This case demonstrates the use of trans-sylvian-transcavernous exposure, rapid ventricular pacing, and thrombectomy amid previous coils and stents to clip a giant, thrombotic basilar apex aneurysm. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
Carotid Stenting: Flow Reversal Technique: 2-Dimensional Operative Video
Authors: Domingo Ricardo A , Ravindran Krishnan , Tawk Rabih G ,   Endovascular Neurosurgery Research Group (ENRG), Arthur Adam , Bain Mark , Bendock Bernard , Jo Binning Mandy , Boulos Alan S , Crowley Webster , Fessler Richard , Grande Andrew , Guterman Lee , Hanel Ricardo , Hoit Daniel , Hopkins L Nelson , Howington Jay , James Robert , Jankowitz Brian , Kan Peter , Khalessi Alex A , Kim Louis , Langer David , Lanzino Giuseppe , Levitt Michael , Levy Elad I , Lopes Demetrius , Mack William , Mericle Robert , Mocco J , Ogilvy Chris , Pandey Aditya , Replogle Robert , Riina Howard , Ringer Andrew , Rodriguez Rafael , Saugaveau Eric , Schirmer Clemens , Siddiqui Adnan H , Spiotta Alex , Sultan Ali , Tawk Rabih , Thomas Ajith , Turner Raymond , Veznedaroglu Erol , Welch Babu , White Jonathan
Published: April 2021

Management options for carotid stenosis include medical management, carotid endarterectomy, carotid stenting with distal filter protection, or stenting with either flow arrest or flow reversal techniques.
1
Flow reversal with transcarotid artery revascularization (TCAR) technique represents a hybrid approach with surgical access to the common carotid for endovascular placement of a stent in the internal carotid artery. This direct access to the carotid artery avoids navigating the challenging anatomy of the aortic arch with endovascular devices.
2
Compared to transfemoral stenting, TCAR possesses lower risk of transient ischemic attack and stroke, and compared to carotid endarterectomy, there is less risk of cranial neuropathy.
3,4

 We present the case of an 87-yr-old man with recurrent severe stenosis (85%) of the right internal carotid artery. The patient had a remote history of bilateral endarterectomies for asymptomatic stenosis and was found with recurrence and progression of right internal carotid artery stenosis. Options were discussed and decision was made to proceed with TCAR after he consented for the procedure. The patient tolerated the procedure well with satisfactory revascularization. Exam remained unremarkable prior to discharge on postoperative day 1 and during follow-up at 1 mo. Patient consented to the publication of their image.
Dissecting Fusiform PICA Aneurysm Repair With Trapping and an Unconventional End-to-Side Reanastomosis: 2-Dimensional Operative Video
Authors: Frisoli Fabio A , Catapano Joshua S , Singh Rohin , Lawton Michael T
Published: April 2021

Dissecting fusiform posterior inferior cerebellar artery (PICA) aneurysms are rare and challenging.
1,2
One common treatment is occlusion of the aneurysm and parent artery via an endovascular approach without revascularization.
3
Revascularization of the artery requires an open microsurgical bypass or endovascular placement of a newer-generation flow diverter.
4
We present an end-to-side reanastomosis of the PICA for treatment of a dissecting fusiform left PICA aneurysm with anatomy deemed unfavorable for endovascular treatment in a 62-yr-old man with subarachnoid hemorrhage. After discussions regarding risks, benefits, and alternatives to the procedure, the family consented to surgical treatment.

 A far-lateral craniotomy was performed, with partial condylectomy to widen the exposure. The cisterna magna was opened, and the dentate ligament was cut to visualize the vertebral artery. The PICA was identified and traced distally to the aneurysmal segment, which was circumferentially diseased. Perforators were noted immediately distal to the aneurysm. The aneurysm was then trapped, and the afferent artery was transected and brought to the sidewall of the distal artery. The recipient site was trapped with temporary clips, and a linear arteriotomy was made. An end-to-side reanastomosis was performed, temporary clips were removed, and hemostasis was achieved. Postoperative angiography confirmed bypass patency and preservation of the PICA perforators.

 Conventional reanastomosis of the parent artery after aneurysm excision is achieved by end-to-end reanastomosis. In contrast, we performed an unconventional end-to-side reanastomosis to revascularize the PICA while leaving the efferent artery in situ to protect its medullary perforators. This bypass is an example of a fourth-generation bypass.
5,6
Used with permission from the Barrow Neurological Institute, Phoenix, Arizona.
Combining quantitative and qualitative magnetic resonance imaging features to differentiate anorectal malignant melanoma from low rectal cancer
Authors: Xu Zeyan , Zhao Ke , Han Lujun , Li Pinxiong , Shi Zhenwei , Huang Xiaomei , Han Chu , Wang Huihui , Chen Minglei , Liu Chen , Liang Yanting , Li Suyun , Huang Yanqi , Chen Xin , Liang Changhong , Cao Wuteng , Liu Zaiyi
Published: April 2021

Background

Distinguishing anorectal malignant melanoma from low rectal cancer remains challenging because of the overlap of clinical symptoms and imaging findings. We aim to investigate whether combining quantitative and qualitative magnetic resonance imaging (MRI) features could differentiate anorectal malignant melanoma from low rectal cancer.

Methods

Thirty-seven anorectal malignant melanoma and 98 low rectal cancer patients who underwent pre-operative rectal MRI from three hospitals were retrospectively enrolled. All patients were divided into the primary cohort (N = 84) and validation cohort (N = 51). Quantitative image analysis was performed on T1-weighted (T1WI), T2-weighted (T2WI), and contrast-enhanced T1-weighted imaging (CE-T1WI). The subjective qualitative MRI findings were evaluated by two radiologists in consensus. Multivariable analysis was performed using stepwise logistic regression. The discrimination performance was assessed by the area under the receiver operating characteristic curve (AUC) with a 95% confidence interval (CI).

Results

The skewness derived from T2WI (T2WI-skewness) showed the best discrimination performance among the entire quantitative image features for differentiating anorectal malignant melanoma from low rectal cancer (primary cohort: AUC = 0.852, 95% CI 0.788–0.916; validation cohort: 0.730, 0.645–0.815). Multivariable analysis indicated that T2WI-skewness and the signal intensity of T1WI were independent factors, and incorporating both factors achieved good discrimination performance in two cohorts (primary cohort: AUC = 0.913, 95% CI 0.868–0.958; validation cohort: 0.902, 0.844–0.960).

Conclusions

Incorporating T2WI-skewness and the signal intensity of T1WI achieved good performance for differentiating anorectal malignant melanoma from low rectal cancer. The quantitative image analysis helps improve diagnostic accuracy.
Safety assessment ofBauhinia cheilanthaBong. Steud leaves extract: acute, sub-acute toxicity, antioxidant, and antihemolytic evaluations
Authors: de Brito Alanne Lucena , Quixabeira Carla Mirele Tabósa , de Lima Lidiane Mâcedo Alves , Paz Silvana Tavares , Gomes Ayala Nara Pereira , de Souza Araújo Thiago Antônio , de Albuquerque Ulysses Paulino , Gomes Dayane Aparecida , Silva Tania Maria Sarmento , Lira Eduardo Carvalho
Published: April 2021

Bauhinia cheilantha (Fabaceae), known popularly as pata-de-vaca and mororó has been largely recommended treating several diseases in folk medicine. However, information on safe doses and use is still scarce. The goal was to evaluate in-vitro antioxidant and antihemolytic and also acute and sub-acute toxicity effects of hydroalcoholic extract from B. cheilantha leaves (HaEBcl). The identification of the compounds in the HaEBcl was performed by ultra-performance liquid chromatography coupled with a diode array detector and quadrupole time-of-flight mass spectrometry. Antioxidant and hemolytic activity of HaEBcl was evaluated in vitro. To study acute toxicity, female mice received HaEBcl in a single dose of 300 and 2.000 mg/kg. Later, sub-acute toxicity was introduced in both female and male mice by oral gavage at 300, 1000, or 2000 mg/kg for 28 consecutive days. Hematological and biochemical profiles were created from the blood as well as from histological analysis of the liver. HaEBcl is rich in flavonoids (quercitrin and afzelin), has no hemolytic effects and moderate antioxidant effects in vitro. Acute toxicity evaluation showed that lethal dose (LD50) of HaEBcl was over 2000 mg/kg. Sub-acute toxicity testing elicited no clinical signs of toxicity, morbidity, or mortality. The hematological and biochemical parameters discounted any chance of hepatic or kidney toxicity. Furthermore, histopathological data did not reveal any disturbance in liver morphology in treated mice. Results indicate that HaEBcl has no hemolytic and moderate antioxidant effects in vitro. In addition, HaEBcl dosage levels up to 2000 mg/kg are nontoxic and can be considered safe for mammals.
Automated Nerve Monitoring in Shoulder Arthroplasty: A Prospective Randomized Controlled Study
Authors: Chui Jason , Chohan Moaz B. Y. , Murkin John M. , Rachinsky Maxim , Dhir Shalini , Athwal George S. , Faber Kenneth J. , Drosdowech Darren
Published: April 2021

Background

Evoked potential monitoring is believed to prevent neurologic injury in various surgical settings; however, its clinical effect has not been scrutinized. It was hypothesized that an automated nerve monitor can minimize intraoperative nerve injury and thereby improve clinical outcomes in patients undergoing shoulder arthroplasty.

Methods

A prospective, blinded, parallel group, superiority design, single-center, randomized controlled study was conducted. Study participants were equally randomized into either the automated nerve-monitored or the blinded monitored groups. The primary outcome was intraoperative nerve injury burden as assessed by the cumulative duration of nerve alerts. Secondary outcomes were neurologic deficits and functional scores of the operative arm, and the quality of life index (Euro Quality of life-5 domain-5 level score) at postoperative weeks 2, 6, and 12.

Results

From September 2018 to July 2019, 213 patients were screened, of whom 200 were randomized. There was no statistically significant difference in the duration of nerve alerts between the automated nerve-monitored and control groups (median [25th, 75th interquartile range]: 1 [0, 18] and 5 [0, 26.5]; Hodges–Lehman difference [95% CI]: 0 [0 to 1] min; P = 0.526). There were no statistically significant differences in secondary outcomes between groups. However, in the ancillary analysis, there were reductions in neurologic deficits and improvements in quality of life index occurring in both groups over the course of the study period.

Conclusions

Protection from nerve injury is a shared responsibility between surgeons and anesthesiologists. Although a progressive improvement of clinical outcomes were observed over the course of the study in both groups as a consequence of the real-time feedback provided by the automated nerve monitor, this trial did not demonstrate that automated nerve monitoring by itself changes important clinical outcomes compared with no monitoring.

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Comprehensive Error Analysis for Robotic-assisted Placement of Pedicle Screws in Pediatric Spinal Deformity: The Initial Learning Curve
Authors: Morse Kyle W. , Heath Madison , Avrumova Fedan , Defrancesco Christopher , Fabricant Peter D. , Lebl Darren R. , Widmann Roger F.
Published: April 2021

Background:

Surgical navigation improves pedicle screw insertion accuracy and reliability. Robotic-assisted spinal surgery and screw placement has not been fully assessed in pediatric patients with spine deformity undergoing posterior spinal fusion. The purpose of this study was to describe the learning curve for robotically assisted pedicle screw placement in pediatric patients.

Methods:

A retrospective review on a consecutive series of the first 19 pediatric patients who underwent posterior spinal fusion by a single surgeon using robotic navigation was performed. Demographics, curve parameters, pedicle diameter, vertebral rotation, and additional outcome measures were recorded. Screw position was assessed with calibrated intraoperative 3-dimensional fluoroscopic images. All complications of planned and placed robotically placed screws were recorded.

Results:

A total of 194 left-sided screws were planned as robot-assisted. One hundred sixty-eight of the robotically planned screws (86.6%) were placed with robot assistance; 29 robotically planned screws (15.0%) were abandoned or converted to freehand. The mean time per robotically placed screw was 3.6±2.4 minutes. Fifteen breaches (8.9%) and 1 anterior perforation occurred with 2 critical (>2 to 4 mm) breaches, 1 was associated with a durotomy, and both occurred in the first case. There were no intraoperative/postoperative neuromonitoring changes and no sequela from the durotomy. Six breaches occurred in the first case. The odds ratio of obtaining a breach in screws with a matched trajectory was 0.275 (95% confidence interval: 0.089-0.848).

Conclusions:

Screw time and accuracy improved and the number of breaches decreased after 10 cases. This series had 2 critical breaches (between 2 and 4 mm) on the first case. Overall, excluding the 2 critical breaches, 98.8% of robotically executed screws were placed without a critical breach, which is comparable to previous pediatric deformity studies. Caution should be exercised during the initial training period to avoid complications as experience and training lead to an improved understanding of surgical planning, skive, and soft-tissue pressure on the end-effector all of which can impact accuracy of robotically assisted pedicle screw placement.

Level of Evidence:

Case Series, IV.
Cartilage Restoration and Use of Orthobiologics
Authors: Camacho Daniel , Mardones Rodrigo
Published: April 2021

Orthobiologics are materials derived from biological substances, which aim to improve regeneration of tissues that are relevant in orthopedic surgery. Platelet-rich plasma, bone marrow, and mesenchymal stem cells are examples of orthobiologics, the use of which has increased explosively in clinical practice in recent years. In this chapter, we review the characteristics and clinical evidence available for this orthobiologics.
Osseointegration
Authors: Sabharwal Samir , Shores Jaimie T. , Forsberg Jonathan A.
Published: April 2021

Osseointegration is a technique that confers a number of advantages to amputees dissatisfied with traditional socket prostheses. An osseointegrated implant consists of a bone-anchored device attached to a patient’s residual limb, and a transdermal component, which connects the external prosthesis. By anchoring into bone, an osseointegrated prosthesis provides direct skeletal attachment, allowing for improved mobility and coordination, gait which more closely approximates a native limb, better proprioception, and obviation of the problems associated with the traditional socket—residuum interface, including poor socket fit and soft tissue irritation. Both the bony and soft tissue work of osseointegration warrant careful consideration. We recommend collaboration between rehabilitation, orthopedic, and plastic surgery teams at each step of the process.
Hsa_circ_0069094 knockdown inhibits cell proliferation, migration, invasion and glycolysis, while induces cell apoptosis by miR-661/HMGA1 axis in breast cancer
Authors: Sui Chao , Qu Wei , Lian Yanfen , Feng Chuanbo , Zhan Yi
Published: April 2021

Circular RNAs (circRNAs) are revealed to regulate breast cancer progression. This study aimed to investigate hsa_circ_0069094-mediated effects on breast cancer cell malignancy. Quantitative real time PCR was employed to evaluate the expressions of hsa_circ_0069094, miR-661 and high mobility group A1 (HMGA1). Western blot was performed to determine the protein expression of HMGA1 and proliferating cell nuclear antigen. Breast cancer malignant progressions were explained by cell counting kit-8 proliferation, cell colony formation, flow cytometry analysis, wound-healing and transwell assays. Cell glycolysis was assessed by detecting glucose take, lactate production and hexokinase 2 (HK2) protein level. The target relationship between miR-661 and hsa_circ_0069094 or HMGA1 was predicted by circular RNA interactome and targetscan online databases, and identified by dual-luciferase reporter and RNA immunoprecipitation assay. The effects of hsa_circ_0069094 knockdown on breast cancer growth in vivo were elucidated by in vivo tumor formation assay. Hsa_circ_0069094 and HMGA1 expression were significantly upregulated, while miR-661 expression level was downregulated in breast cancer tissues and cells relative to adjacent normal breast tissues or MCF-10A cells. Functionally, hsa_circ_0069094 knockdown inhibited cell glycolysis, proliferation, migration and invasion, whereas induced cell apoptosis in breast cancer, which was decreased by miR-661 inhibitor. Mechanistically, hsa_circ_0069094 regulated HMGA1 by sponging miR-661. Furthermore, hsa_circ_0069094 knockdown repressed tumor formation in vivo. Collectively, hsa_circ_0069094 knockdown repressed breast cancer cell carcinogenesis and cell glycolysis by regulating HMGA1 through sponging miR-661, which provided a new insight for studying the mechanism of hsa_circ_0069094 in modulating breast cancer development.
LFZ-4-46, a tetrahydroisoquinoline derivative, induces apoptosis and cell cycle arrest via induction of DNA damage and activation of MAPKs pathway in cancer cells
Authors: Xu Lili , Huang Guozheng , Zhu Zhihui , Tian Shasha , Wei Yingying , Hong Huanwu , Lu Xiaowei , Li Ying , Liu Feize , Zhao Huajun
Published: April 2021

LFZ-4-46, that is [2-hydroxy-1-phenyl-1,5,6,10b-tetrahydropyrazolo(5,1-a) isoquinolin-3(2H)-yl](phenyl) methanone, a tetrahydroisoquinoline derivative with a pyrazolidine moiety, was synthetically prepared. The anti-cancer mechanism of the compound has not been clarified yet. In this study, the anticancer effects and potential mechanisms of LFZ-4-46 on human breast and prostate cancer cells were explored. (a) 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazoliumbromide assay was first performed to detect the effects of LFZ-4-46 on the viability of human cancer cells. (b) Comet assay was utilized to evaluate DNA damage. (c) Cell cycle, apoptosis and mitochondrial membrane potential were detected by flow cytometry. (d) The expression of relative proteins was detected by western blotting assay. LFZ-4-46 significantly inhibited the viability of cancer cells in a time- and dose-dependent manner and had no obviously inhibitory effect on the viability of mammary epithelial MCF-10A cells. Mechanistic studies demonstrated that LFZ-4-46-induced cell apoptosis and cycle arrest were mediated by DNA damage. It caused DNA damage through activating γ-H2AX and breaking DNA strands. Further studies showed that mitogen-activated protein kinasess pathway was involved in these activated several key molecular events. Finally, LFZ-4-46 showed a potent antitumor effect in vivo. These results suggest that LFZ-4-46 may be a potential lead compound for the treatment of breast and prostate cancer.
miR-5701 promoted apoptosis of clear cell renal cell carcinoma cells by targeting phosphodiesterase-1B
Authors: Zhao Changan , Mo Liping , Lei Ting , Yan Yan , Han Shuiping , Miao Jiyu , Gao Yi , Wang Xiaofei , Zhao Wenbao , Huang Chen
Published: April 2021

Increasing evidence has demonstrated that microRNAs play critical roles in malignant biological behaviors, including cancerogenesis, cancer progression and metastasis, through the regulation of target genes expression. As miR-5701 has recently been identified to play roles as tumor suppressor miRNA in the development of some kinds of cancers, in this study we sought to investigate the role of miR-5701 in clear cell renal cell carcinoma (ccRCC). Colony formation, cell apoptosis and proliferation assays were employed, and the results showed that miR-5701 inhibited proliferation and promoted apoptosis of ccRCC cells. Western blotting and dual-luciferase reporter assays were used to confirm that PDE1B is a new direct target of miR-5701. Furthermore, overexpression of PDE1B attenuated the effects of miR-5701, indicating that miR-5701 inhibited proliferation and promoted apoptosis of ccRCC cells via targeting PDE1B. Taken together, the data presented here indicate that t miR-5701 is a tumor suppressor in ccRCC and PDE1B is a new target of miR-5701.
Hopes and failures in front-line advanced HER2-positive gastric cancer therapy
Authors: Kong Fanming , Yao Yang , Deng Renfen , Li Xiaojiang , Jia Yingjie
Published: April 2021

Human epidermal growth-factor receptor 2 (HER2) was an important therapeutic target in gastric cancer. Through the last decade, strategy with trastuzumab-based chemotherapy remains the first-line standard of treatment in advanced HER2-positive gastric cancer. Based on the Trastuzumab for Gastric Cancer trial, trastuzumab plus systemic chemotherapy of cisplatin and fluoropyrimidine as the backbone was established as the first-line therapy in advanced HER2-positive gastric cancer. Since then, studies have explored the optimization of the front-line strategy, including the dose of trastuzumab, chemotherapy regimen and maintenance therapy. A large number of clinical trials were conducted to explore the optimal front-line therapy regimens, such as lapatinib and pertuzumab. Safe and effective first-line regimens are still lacking. Recently, two phase II studies of combining immune checkpoint inhibitor in first-line treatment of advanced HER2-positive gastric cancer showed promising results. The progress of immunotherapy has gradually promoted the development of front-line treatment of advanced HER2-positive gastric cancer to potential chemotherapy-free strategies. Therefore, this article reviewed these significant clinical trials and focus on the front-line treatment strategies for HER2-positive gastric cancer.
Silencing of circ_0078607 prevents development of gastric cancer and inactivates the ERK1/2/AKT pathway through the miR-188-3p/RAP1B axis
Authors: Bian Weixin , Liu Zhiqiang , Chu Yanjie , Xing Xiaofang
Published: April 2021

The aim of this study is to explore the expression and mechanism of circ_0078607 on proliferation and apoptosis of gastric cancer. Real time PCR (RT-PCR) was performed to detect the expression of circ_0078607 in gastric cancer tumor tissues, plasma and cell lines. Cell viability was detected by cell counting Kit-8. Cell proliferation ability was assessed by cell cycle assay. The samples were analyzed by flow cytometry for the detection of apoptosis. Luciferase assay and RNA immunoprecipitation (RIP) were carried out to verify the relationship between circ_0078607 and miR-188-3p, miR-188-3p, and RAP1B. Western blot was employed to detect the protein level of RAP1B, ERK1/2 and AKT. In vivo, the effect of circ_0078607 on gastric cancer tumor growth was detected by lentivirus vector injection. Here, we found the increased level of circ_0078607 in gastric cancer tissues, gastric cancer patients plasma and cell lines. Knockdown of circ_0078607 could prevent proliferation and induce cell apoptosis in MKN-28 cells. Then we verified that circ_0078607 could interact with miR-188-3p by performed luciferase assay and RIP. Furthermore, we observed that RAP1B was a potential target of miR-188-3p. Next, we found that miR-188-3p inhibitor or overexpression of RAP1B could prevent the anti-tumor function of sh-circ_0078607. Silencing of circ_0078607 inhibited ERK1/2/AKT signal pathways via regulating miR-188-3p/RAP1B. In vivo, knockdown of circ_0078607 inhibited tumor growth. Knockdown of circ_0078607 inhibits the proliferation and induces apoptosis of gastric cancer via miR-188-3p/RAP1B signal pathway.