bluuebunny/crossref_metadata_2025 huggingface dataset:
Challenges in Oncologic Preparedness: A Retrospective Review of Incident Surgical Cancers During Pacific Partnership Missions, 2008-2016
Authors: Reichl Allison , Schutt Ryan , Walsh John , Prieto James , Sykes Alicia G , Bickler Stephen , Ignacio Romeo
Published: December 2020

Introduction

For over 30 years, the USNS Mercy hospital ship has provided surgical care on multiple humanitarian aid and disaster relief missions. During these missions, surgical support varies according to host nation needs, and the operative treatment of cancer patients remains controversial. We report the number of incidentally discovered surgical oncologic cases treated aboard the USNS Mercy on four missions and discuss challenges regarding oncologic care on these missions.

Materials and Methods

Between 2008 and 2016, operative cases and surgical pathology results from four multinational humanitarian missions were analyzed according to organ system, patient’s geographic location, and diagnosis. Primary outcomes were total number and proportion of malignant cases, analyzed yearly and over all four missions. Secondary outcomes were malignant diagnoses by organ system and host nation health capacities (based on indicators from the WHO).

Results

A total of 2,767 operations were performed during 18 port visits in 8 countries in Southeast Asia. In total, 1,193 pathology specimens (surgical biopsies, fine needle aspirations, etc.) were obtained. Overall malignancy rate across all organ systems was 9%. Yearly malignancy rates ranged from 2% to 13%. The highest malignancy rates were found in thyroid (33%), breast (20%), and parotid and salivary gland cases (19%). All host nations had operational strategies for cancer in place (n = 8, 100%), but few had national infrastructures to treat noncommunicable diseases (n = 2, 25%).

Conclusions

Despite current policies to screen out cancer patients on USNS Mercy missions, 9% of surgical biopsies were malignant. Cancer management during these missions presents a unique challenge because of limited resources for surgery, chemoradiotherapy, and follow-up care. Contingency plans must be considered to provide completion of care for these patients whose cancers are discovered incidentally. Furthermore, an understanding of host nation capabilities in relation to medical and surgical care is crucial to providing treatment in resource-limited areas.
The Glossopharyngo-Cochlear Triangle—Part II: Case Series Highlighting the Clinical Application to High-Riding Posterior Inferior Cerebellar Artery Aneurysms Exposed Through the Extended Retrosigmoid Approach
Authors: Baranoski Jacob F , Koester Stefan W , Przybylowski Colin J , Zhao Xiaochun , Catapano Joshua S , Gandhi Sirin , Tayebi Meybodi Ali , Cole Tyler S , Lee Jonathan , Frisoli Fabio A , Lawton Michael T , Mascitelli Justin R
Published: December 2020

BACKGROUND

Use of the far lateral transcondylar (FL) approach and vagoaccessory triangle is the standard exposure for clipping most posterior inferior cerebellar artery (PICA) aneurysms. However, a distal PICA origin or high-lying vertebrobasilar junction can position the aneurysm beyond the vagoaccessory triangle, making the conventional FL approach inappropriate.

OBJECTIVE

To demonstrate the utility of the extended retrosigmoid (eRS) approach and a lateral trajectory through the glossopharyngo-cochlear triangle as the surgical corridor for these cases.

METHODS

High-riding PICA aneurysms treated by microsurgery were retrospectively reviewed, comparing exposure through the eRS and FL approaches. Clinical, surgical, and outcome measures were evaluated. Distances from the aneurysm neck to the internal auditory canal (IAC), jugular foramen, and foramen magnum were measured.

RESULTS

Six patients with PICA aneurysms underwent clipping using the eRS approach; 5 had high-riding PICA aneurysms based on measurements from preoperative computed tomography angiography (CTA). Mean distances of the aneurysm neck above the foramen magnum, below the IAC, and above the jugular foramen were 27.0 mm, 3.7 mm, and 8.2 mm, respectively. Distances were all significantly lower versus the comparison group of 9 patients with normal or low-riding PICA aneurysms treated using an FL approach (P < .01). All 6 aneurysms treated using eRS were completely occluded without operative complications.

CONCLUSION

The eRS approach is an important alternative to the FL approach for high-riding PICA aneurysms, identified as having necks more than 23 mm above the foramen magnum on CTA. The glossopharyngo-cochlear triangle is another important anatomic triangle that facilitates microsurgical dissection.
A Case Series of Surgically Treated Spinal Dumbbell Tumors of Critical Parent Nerve Roots: To Cut or Not to Cut?
Authors: Butenschoen Vicki Marie , Kögl Nikolaus , Meyer Bernhard , Thomé Claudius , Wostrack Maria
Published: December 2020

BACKGROUND

Dumbbell tumors present challenging cases, with either an incomplete tumor resection or a need to sacrifice nerve roots. Published literature suggests encouraging neurological outcomes after nerve root amputation.

OBJECTIVE

To determine the incidence of postoperative neurological deficits after amputating the parent nerve root.

METHODS

A retrospective consecutive analysis of all patients treated for dumbbell nerve sheet tumors with a reported amputation of the functional relevant parent nerve roots C5-Th1 and L3-S1.

RESULTS

Among 21 evaluated patients, minor postoperative neurological motor function deterioration occurred in 4 patients (19%). Most patients recovered to the preoperative level at the follow-up examination, and only one patient retained a new Medical Research Council (MRC) scale of 4/5 for deltoid weakness. The majority of tumors were resected at the lumbar level (nerve root L3: 28.6%, L5: 19%). Gross total resection was achieved in 90.5% of patients. Neuropathic pain was reported in one third of the patients during the long-term follow-up.

CONCLUSION

Amputating critical parent nerve roots during the dumbbell tumor resections seems to result in a low incidence of postoperative motor deficits and may offer an acceptable sacrifice in otherwise only incompletely resectable dumbbell tumors. The cross-innervation of neighboring nerve roots and its, probably, per-se-reduced functionality may be a possible mechanism for maintaining motor function.
Retroperitoneal Exposure of the Anterior Lumbar Spine
Authors: Burkett Daniel J , Burkett Jeffrey S
Published: December 2020

BACKGROUND

Anterior lumbar spine procedures such as anterior lumbar interbody fusion (ALIF) are used commonly to treat multiple pathologies, including pseudoarthrosis and degenerative disk disease. It is generally a safe and effective procedure, but an anterior approach to the lumbar spine requires critical navigation of the surgical window to avoid delicate structures. An operative technique should maximize the exposure without an increased risk of iatrogenic injury.

OBJECTIVE

To describe in detail a retroperitoneal exposure of the anterior lumbar spine.

METHODS

This surgical approach is a unique variation of standard anterior lumbar spine exposure techniques. This technique is described and illustrated in detail with an accompanying Supplemental Digital Content: video. Institutional Review Board (IRB) approval was not required because this is a variation of current techniques. Patient consent was obtained for the procedure and use of operative pictures and videos.

RESULTS

Precise details of the technique are described. The surgical video demonstrates the technique for the L5-S1 ALIF approach.

CONCLUSION

This technique is a novel variation of the standard retroperitoneal exposure of the anterior lumbar spine. The incision placement, size, and dynamic blunt retraction of this approach limit tissue disruption and provide an efficient exposure that has not been previously described in the literature.
Fenestration of Symptomatic Ventriculus Terminalis: 2-Dimensional Operative Video
Authors: Helal Ahmed , Pirina Alessandro , Sorenson Thomas J , Palandri Giorgio
Published: December 2020

This is a case of a 73 yr-old female presenting with low back pain and bilateral sciatic pain, which progressed to bilateral lower extremity weakness about 1 yr after initial presentation. Imaging of her thoraco-lumbar spine revealed a ventriculus terminalis extending from the level of the eleventh thoracic vertebra (T11) to the first lumbar vertebra (L1). Ventriculus terminalis is an embryological ependymal lined cavity that normally regresses with development. In individuals with persistent ventriculus terminalis, it is usually incidentally noted during spine imaging for other purposes. Surgery is seldom indicated except for patients presenting with progressive neurological deficits. Patient was taken to surgery for fenestration of the ventriculus and decompression of the spinal canal. The patient was positioned prone, and after proper localization the vertebral column was exposed through a midline approach and a central laminectomy was performed from T11-L1. Intraoperative monitoring was used throughout the procedure. This video illustrates the gross appearance of a ventriculus terminalis, dissection of surrounding neural elements, and decompression of the ventriculus using a wide fenestration technique.

 All relevant patient identifiers have been removed from the video. Nevertheless, patient consent was obtained regarding video recording and redistribution of procedure for educational purposes.
Single- versus Dual-Attending Surgeon Approach for Spine Deformity: A Systematic Review and Meta-Analysis
Authors: Lak Asad M , Abunimer Abdullah M , Goedmakers Caroline M W , Aglio Linda S , Smith Timothy R , Makhni Melvin , Mekary Rania A , Zaidi Hasan A
Published: December 2020

BACKGROUND

Surgical management of spine deformity is associated with significant morbidity. Recent literature has inconsistently demonstrated better outcomes after utilizing 2 attending surgeons for spine deformity.

OBJECTIVE

To conduct a systematic review and meta-analysis on studies reporting outcomes following single- vs dual-attending surgeons for spine deformity.

METHODS

MEDLINE, Embase, Web of science, and Cochrane databases were last searched on July 16, 2020. A total of 1013 records were identified excluding duplicates. After screening, 10 studies (4 cohort, 6 case series) were included in the meta-analysis. Random-effect models were used to pool the effect estimates by study design. When feasible, further subgroup analysis by deformity type was conducted.

RESULTS

A total of 953 patients were analyzed. Pooled results from propensity score-matched cohort studies revealed that the single-surgeon approach was unfavorably associated with a nonstatistically significant higher blood loss (mean difference = 421.0 mL; 95% CI: −28.2, 870.2), a statistically significant higher operative time (mean difference = 94.3 min; 95% CI: 54.9, 133), length of stay (mean difference = 0.84 d; 95% CI: 0.46, 1.22), and an increased risk of complications (Mantel-Haenszel risk ratio = 2.93; 95% CI: 1.12, 7.66). Data from pooled case series demonstrated similar results for all outcomes. Moreover, these results did not differ significantly between deformity types (adolescent idiopathic scoliosis and adult spinal deformity).

CONCLUSION

Dual-attending surgeon approach appeared to be associated with reduced operative time, shorter hospital stays, and reduced risk of complications. These findings may potentially improve outcomes in surgical treatment of spine deformity.
Construction, characterization and crystal structure of a fluorescent single-chain Fv chimera
Authors: Velappan Nileena , Close Devin , Hung Li-Wei , Naranjo Leslie , Hemez Colin , DeVore Natasha , McCullough Donna K , Lillo Antonietta M , Waldo Geoffrey S , Bradbury Andrew R M
Published: December 2020

In vitro display technologies based on phage and yeast have a successful history of selecting single-chain variable fragment (scFv) antibodies against various targets. However, single-chain antibodies are often unstable and poorly expressed in Escherichia coli. Here, we explore the feasibility of converting scFv antibodies to an intrinsically fluorescent format by inserting the monomeric, stable fluorescent protein named thermal green, between the light- and heavy-chain variable regions. Our results show that the scTGP format maintains the affinity and specificity of the antibodies, improves expression levels, allows one-step fluorescent assay for detection of binding and is a suitable reagent for epitope binning. We also report the crystal structure of an scTGP construct that recognizes phosphorylated tyrosine on FcεR1 receptor of the allergy pathway.
Smoking during pregnancy: changes and associated risk factors in Spain, 1980-2016
Authors: Salinas-Vilca Ana , Cuevas Lourdes ,   ECEMC Peripheral Group, Bermejo-Sánchez Eva , Galán Iñaki
Published: December 2020

Background

Trends for maternal smoking rates have varied substantially across industrialized countries. The objective was to describe how the prevalence of maternal smoking evolved in Spain during 1980–2016.

Methods

Data came from the Spanish Collaborative Study of Congenital Malformations. Our sample consisted of 40 934 mothers of newborns with no congenital defects from hospitals all across Spain. We estimated change points in trend and the mean annual change in smoking prevalence using ‘joinpoint’ regression. Relevant potential factors (age, country of birth, education, parity, planned pregnancy and alcohol consumption) were examined using multivariate logistic regression.

Results

Maternal smoking prevalence in 1980 and 2016 were 14.3% (95% confidence interval [CI]: 11.9–17.0) and 20.4% (95% CI: 15.9–25.8). We identified four periods with distinct trends: a sharp increase during the 80s, a plateau during the 90s, a decrease starting in 2000 and a slowdown of such decrease from 2009 on. Smoking was significantly higher among young women, Spain-born, with low education, unplanned pregnancy, and alcohol consumption.

Conclusions

Currently in Spain maternal smoking remains very high. Tobacco consumption trend showed an increase during the 80s, a plateau during the 90s, and a reduction in the 2000s. Several sociodemographic and behavioural factors were associated to greater likelihood of smoking.
Neurological Soft Signs Are Associated With Altered Cerebellar-Cerebral Functional Connectivity in Schizophrenia
Authors: Cai Xin-Lu , Wang Yong-Ming , Wang Yi , Zhou Han-Yu , Huang Jia , Wang Ya , Lui Simon S Y , Møller Arne , Hung Karen S Y , Mak Henry K F , Sham Pak C , Cheung Eric F C , Chan Raymond C K
Published: December 2020

Cerebellar dysfunction is associated with neurological soft signs (NSS), which is a promising endophenotype for schizophrenia spectrum disorders. However, the relationship between cerebellar-cerebral resting-state functional connectivity (rsFC) and NSS is largely unexplored. Moreover, both NSS and cerebellar-cerebral rsFC have been found to be correlated with negative symptoms of schizophrenia. Here, we investigated the correlations between NSS and cerebellar-cerebral rsFC, explored their relationship with negative symptoms in a main dataset, and validated the significant findings in a replication dataset. Both datasets comprised schizophrenia patients and healthy controls. In schizophrenia patients, we found positive correlations between NSS and rsFC of the cerebellum with the inferior frontal gyrus and the precuneus, and negative correlations between NSS and rsFC of the cerebellum with the inferior temporal gyrus. In healthy controls, NSS scores were positively correlated with rsFC of the cerebellum with the superior frontal gyrus and negatively correlated with rsFC between the cerebellum and the middle occipital gyrus. Cerebellar-prefrontal rsFC was also positively correlated with negative symptoms in schizophrenia patients. These findings were validated in the replication dataset. Our results suggest that the uncoupling of rsFC between the cerebellum and the cerebral cortex may underlie the expression of NSS in schizophrenia. NSS-related cerebellar-prefrontal rsFC may be a potential neural pathway for possible neural modulation to alleviate negative symptoms.
Identification of a Putative DNA-Binding Protein in Arabidopsis That Acts as a Susceptibility Hub and Interacts With Multiple Pseudomonas syringae Effectors
Authors: Schreiber Karl J. , Lewis Jennifer D.
Published: December 2020

Phytopathogens use secreted effector proteins to suppress host immunity and promote pathogen virulence, and there is increasing evidence that the host-pathogen interactome comprises a complex network. To identify novel interactors of the Pseudomonas syringae effector HopZ1a, we performed a yeast two-hybrid screen that identified a previously uncharacterized Arabidopsis protein that we designate HopZ1a interactor 1 (ZIN1). Additional analyses in yeast and in planta revealed that ZIN1 also interacts with several other P. syringae effectors. We show that an Arabidopsis loss-of-function zin1 mutant is less susceptible to infection by certain strains of P. syringae, while overexpression of ZIN1 results in enhanced susceptibility. Functionally, ZIN1 exhibits topoisomerase-like activity in vitro. Transcriptional profiling of wild-type and zin1 Arabidopsis plants inoculated with P. syringae indicated that while ZIN1 regulates a wide range of pathogen-responsive biological processes, the list of genes more highly expressed in zin1 versus wild-type plants is particularly enriched for ribosomal protein genes. Altogether, these data illuminate ZIN1 as a potential susceptibility hub that interacts with multiple effectors to influence the outcome of plant-microbe interactions.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Perineural Liposomal Bupivacaine Is Not Superior to Nonliposomal Bupivacaine for Peripheral Nerve Block Analgesia
Authors: Hussain Nasir , Brull Richard , Sheehy Brendan , Essandoh Michael K. , Stahl David L. , Weaver Tristan E. , Abdallah Faraj W.
Published: December 2020

Background

Liposomal bupivacaine is purported to extend analgesia of peripheral nerve blocks when administered perineurally. However, evidence of the clinical effectiveness of perineural liposomal bupivacaine is mixed. This meta-analysis seeks to evaluate the effectiveness of perineural liposomal bupivacaine in improving peripheral nerve block analgesia as compared with nonliposomal local anesthetics.

Methods

The authors identified randomized trials evaluating the effectiveness of peripheral nerve block analgesic that compared liposomal bupivacaine with nonliposomal local anesthetics. The primary outcome was the difference in area under the receiver operating characteristics curve (AUC) of the pooled 24- to 72-h rest pain severity scores. Secondary outcomes included postoperative analgesic consumption, time to first analgesic request, incidence of opioid-related side effects, patient satisfaction, length of hospital stay, liposomal bupivacaine side effects, and functional recovery. AUC pain scores were interpreted in light of a minimal clinically important difference of 2.0 cm · h.

Results

Nine trials (619 patients) were analyzed. When all trials were pooled, AUC pain scores ± SD at 24 to 72 h were 7.6 ± 4.9 cm · h and 6.6 ± 4.6 cm · h for nonliposomal and liposomal bupivacaine, respectively. As such, perineural liposomal bupivacaine provided a clinically unimportant benefit by improving the AUC (95% CI) of 24- to 72-h pain scores by 1.0 cm · h (0.5 to 1.6; P = 0.003) compared with nonliposomal bupivacaine. Excluding an industry-sponsored trial rendered the difference between the groups nonsignificant (0.7 cm · h [−0.1 to 1.5]; P = 0.100). Secondary outcome analysis did not uncover any additional benefits to liposomal bupivacaine in pain severity at individual timepoints up to 72 h, analgesic consumption, time to first analgesic request, opioid-related side effects, patient satisfaction, length of hospital stay, and functional recovery. No liposomal bupivacaine side effects were reported.

Conclusions

Perineural liposomal bupivacaine provided a statistically significant but clinically unimportant improvement in the AUC of postoperative pain scores compared with plain local anesthetic. Furthermore, this benefit was rendered nonsignificant after excluding an industry-sponsored trial, and liposomal bupivacaine was found to be not different from plain local anesthetics for postoperative pain and all other analgesic and functional outcomes. High-quality evidence does not support the use of perineural liposomal bupivacaine over nonliposomal bupivacaine for peripheral nerve blocks.

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Factors Associated with Improved Quality of Life Outcomes in Patients Undergoing Surgery for Adult Spinal Deformity
Authors: Arima Hideyuki , Hasegawa Tomohiko , Yamato Yu , Togawa Daisuke , Yoshida Go , Yasuda Tatsuya , Banno Tomohiro , Oe Shin , Mihara Yuki , Ushirozako Hiroki , Yamada Tomohiro , Watanabe Yuh , Ide Koichiro , Nakai Keiichi , Matsuyama Yukihiro
Published: December 2020

Study Design.

Retrospective longitudinal cohort study.

Objective.

This study aimed to elucidate factors affecting the likelihood of achieving minimum clinically important difference (MCID) to patient-reported outcomes defined by the Scoliosis Research Society-22r (SRS-22r) among patients with adult spinal deformity (ASD) who underwent extensive corrective fusion surgery from the thoracic spine to the pelvis.

Summary of Background Data.

Achieving MCID for SRS-22r parameters was a measure of surgical efficacy. Patient characteristics and surgical and radiographic factors that affect the likelihood of achieving MCID for SRS-22r parameters are unknown.

Methods.

Data from patients with ASD who underwent extensive corrective fusion surgery from the thoracic spine to the pelvis during 2010 to 2016 were retrospectively reviewed. Data from a total of 167 patients with ≥2 years of follow-up were included. Multivariate analysis was used to investigate factors associated with the likelihood of achieving MCID for each of the SRS-22r domains (Function, Pain, Subtotal) 2 years after surgery. The following MCID values were used: 0.90 for Function, 0.85 for Pain, and 1.05 for the Subtotal.

Results.

MCID achievement rate was 36.5% for Function, 46.1% for Pain, and 44.3% for the Subtotal domain. In multivariate analysis, preoperative SRS-22r Function (odds ratio [OR] = 0.204, 95% confidence interval [CI] 0.105–0.396) increased the likelihood of achieving MCID for SRS-22r Function. Preoperative SRS-22r Subtotal (OR = 0.211, 95% CI, 0.107–0.413), preoperative pelvic tilt (OR = 1.072, 95% CI, 1.012–1.136), preoperative pelvic incidence minus lumbar lordosis (OR = 0.965, 95% CI, 0.934–0.997), and postoperative sagittal vertical axis (OR = 0.985, 95% CI, 0.974–0.995) affected the likelihood of achieving MCID for the SRS-22r Subtotal.

Conclusion.

Patients with poor preoperative health-related quality of life were more likely to achieve improvement in SRS-22r parameters after extensive corrective fusion surgery for ASD. Achieving postoperative sagittal alignment increased the likelihood of achieving MCID for the SRS-22r Subtotal domain.

Level of Evidence: 3
Application of Cooperative Game Theory Principles to Interpret Machine Learning Models of Nonhome Discharge Following Spine Surgery
Authors: Martini Michael L. , Neifert Sean N. , Oermann Eric K. , Gilligan Jeffrey T. , Rothrock Robert J. , Yuk Frank J. , Gal Jonathan S. , Nistal Dominic A. , Caridi John M.
Published: December 2020

Study Design.

Retrospective analysis of prospectively acquired data.

Objective.

The aim of this study was to identify interaction effects that modulate nonhome discharge (NHD) risk by applying coalitional game theory principles to interpret machine learning models and understand variable interaction effects underlying NHD risk.

Summary of Background Data.

NHD may predispose patients to adverse outcomes during their care. Previous studies identified potential factors implicated in NHD; however, it is unclear how interaction effects between these factors contribute to overall NHD risk.

Methods.

Of the 11,150 reviewed cases involving procedures for degenerative spine conditions, 1764 cases (15.8%) involved NHD. Gradient boosting classifiers were used to construct predictive models for NHD for each patient. Shapley values, which assign a unique distribution of the total NHD risk to each model variable using an optimal cost-sharing rule, quantified feature importance and examined interaction effects between variables.

Results.

Models constructed from features identified by Shapley values were highly predictive of patient-level NHD risk (mean C-statistic = 0.91). Supervised clustering identified distinct patient subgroups with variable NHD risk and their shared characteristics. Focused interaction analysis of surgical invasiveness, age, and comorbidity burden suggested age as a worse risk factor than comorbidity burden due to stronger positive interaction effects. Additionally, negative interaction effects were found between age and low blood loss, indicating that intraoperative hemostasis may be critical for reducing NHD risk in the elderly.

Conclusion.

This strategy provides novel insights into feature interactions that contribute to NHD risk after spine surgery. Patients with positively interacting risk factors may require special attention during their hospitalization to control NHD risk.

Level of Evidence: 3
Challenges and Perspectives for Therapeutic Targeting of Myeloproliferative Neoplasms
Authors: Brkic Sime , Meyer Sara C.
Published: December 2020

Myeloproliferative neoplasms (MPNs) are hematopoietic stem cell disorders with dysregulated myeloid blood cell production and propensity for transformation to acute myeloid leukemia, thrombosis, and bleeding. Acquired mutations in JAK2, MPL, and CALR converge on hyperactivation of Janus kinase 2 (JAK2) signaling as a central feature of MPN. Accordingly, JAK2 inhibitors have held promise for therapeutic targeting. After the JAK1/2 inhibitor ruxolitinib, similar JAK2 inhibitors as fedratinib are entering clinical use. While patients benefit with reduced splenomegaly and symptoms, disease-modifying effects on MPN clone size and clonal evolution are modest. Importantly, response to ruxolitinib may be lost upon treatment suggesting the MPN clone acquires resistance. Resistance mutations, as seen with other tyrosine kinase inhibitors, have not been described in MPN patients suggesting that functional processes reactivate JAK2 signaling. Compensatory signaling, which bypasses JAK2 inhibition, and other processes contribute to intrinsic resistance of MPN cells restricting efficacy of JAK2 inhibition overall. Combinations of JAK2 inhibition with pegylated interferon-α, a well-established therapy of MPN, B-cell lymphoma 2 inhibition, and others are in clinical development with the potential to enhance therapeutic efficacy. Novel single-agent approaches targeting other molecules than JAK2 are being investigated clinically. Special focus should be placed on myelofibrosis patients with anemia and thrombocytopenia, a delicate patient population at high need for options. The extending range of new treatment approaches will increase the therapeutic options for MPN patients. This calls for concomitant improvement of our insight into MPN biology to inform tailored therapeutic strategies for individual MPN patients.
OPTIC DISK PIT ASSOCIATED WITH AN UNUSUAL OUTER RETINAL HOLE AND NASAL PERIPHERAL RETINOSCHISIS
Authors: Corvi Federico , Nguyen Tieu Vy , Juhn Alexander , Corradetti Giulia , Al-Sheikh Mayss , Zweifel Sandrine A. , Sadda SriniVas R.
Published: December 2020

Purpose:

To document a peculiar case of optic disk pit-associated maculopathy with extensive nasal retinoschisis with lamellar outer retinal hole.

Methods:

A 41-year-old woman presented to the eye clinic complaining of new photopsias and enlargement of the blind spot in the left eye. Uncorrected visual acuity was 20/20 in both eyes. Fundus examination of the left eye revealed an anomalous appearing optic nerve with a gray oval depression at the temporal margin of the disk consistent with an optic disk pit.

Results:

Optical coherence tomography confirmed the presence of the pit and demonstrated outer plexiform layer schisis superonasal to the fovea and extensive inner and outer retinal schisis nasal to the nerve extending to the equator. A large lamellar outer retinal hole was noted nasal to the disk without associated retinal detachment. The vitreous appeared to be attached over the nasal retina.

Conclusion:

Multimodal imaging revealed an unusual optic disk pit-associated retinopathy with dramatically more extensive retinoschisis and a lamellar outer retinal hole nasal to the nerve despite the temporal location of the pit. Although the precise pathophysiologic mechanisms are not fully understood, forces associated with the vitreo-retinal adhesion may have contributed to the distribution of the schisis in this case.
FOCAL RETINAL ISCHEMIA REVEALED BY MULTIMODAL IMAGING AFTER TRAUMATIC PARTIAL OPTIC NERVE AVULSION
Authors: Van Brummen Alexandra , Mustafi Debarshi , Chee Yewlin E.
Published: December 2020

Purpose:

Traumatic optic neuropathy can have varying presentations. Blunt focal trauma can lead to optic nerve avulsion with underlying retinal findings. A case of partial optic nerve avulsion after finger poke injury leading to focal retinal ischemia is reported.

Methods:

Visual acuity, fundus photography with fluorescein angiography, and spectral-domain optical coherence tomography were performed to document the findings in a 16-year-old man who presented after a finger poke injury to the left orbit during a water polo match.

Results:

On initial presentation, examination revealed decreased visual acuity with a fixed left pupil and afferent pupillary defect by reverse. On slit-lamp examination of the left eye, a hyphema was present. Dilated fundus examination revealed layering vitreous hemorrhage over the posterior pole and an avulsed vitreous base. On follow-up, a gap temporal to the optic nerve head consistent with a partial optic nerve avulsion was noted once the vitreous hemorrhage cleared. Multimodal imaging revealed retinal ischemia temporal to the disc on fluorescein angiography with corresponding changes in the inner retinal layers and retinal nerve fiber layer using spectral-domain optical coherence tomography.

Conclusion:

Clinicians should have a high suspicion for optic nerve avulsion if a patient presents with new vitreous hemorrhage and afferent pupillary defect after a finger-poke injury. Optic nerve avulsion injury can cause retinal ischemia, likely because of interruption of retinal blood flow as a result of nerve shearing injury. Multimodal imaging can reveal focal retinal injury and aid in proper diagnosis and follow-up.
Automated control of fraction of inspired oxygen: is it time for widespread adoption?
Authors: Mitra Souvik , McMillan Douglas
Published: December 2020

Purpose of review

Over the past two decades, numerous algorithms for automated control of the fraction of inspired oxygen (FiO2) have been developed and incorporated into contemporary neonatal ventilators and high-flow devices in an attempt to optimize supplemental oxygen therapy in preterm infants. This review explores whether current evidence is sufficient to recommend widespread adoption of automated oxygen control in neonatal care.

Recent findings

To date, 15 studies have compared automated versus manual control of FiO2 in preterm infants on respiratory support. This includes four new randomized cross-over trials published in the last 2 years. Available evidence consistently demonstrates a significant improvement in time spent within the target saturation range with automated FiO2 control. There are fewer episodes of severe hypoxemia and fewer manual FiO2 adjustments with automated oxygen control. Nursing workload may be reduced. However, no currently completed studies report on clinical outcomes, such as chronic lung disease or retinopathy of prematurity.

Automated oxygen control appears to be a reasonable option for FiO2 titration in preterm infants on respiratory support, if resources are available, and might substantially reduce nursing workload. Further randomized clinical trials to explore its effects on clinical outcomes are required.
When should we use corticosteroids in severe community-acquired pneumonia?
Authors: Póvoa Pedro , Coelho Luís , Salluh Jorge
Published: December 2020

Purpose of review

This review aims to evaluate the evidence and recommendations for the prescription of corticosteroids as adjunctive therapy in patients with severe community-acquired pneumonia.

Recent findings

Corticosteroids have been prescribed with the objective to attenuate the marked and persistent activation of the immune system. However, some causes of community-acquired pneumonia, namely viral, are associated with unexpected low levels of cytokines and depressed cellular immunity. As a result, several recent randomized controlled trials and large prospective observational studies repeatedly showed that corticosteroids had no impact on survival, and in some types of pneumonia like influenza, its use was associated with potential harmful effects like invasive aspergillosis. Apart from this, adverse effects, namely hyperglycemia, superinfections and increased length-of-stay, were frequent findings in the corticosteroid-treated patients.

According to the current evidence, corticosteroids are recommended in Pneumocystis jiroveci pneumonia in HIV-infected patients and recommendations are against its use in influenza. In all other forms of severe community-acquired pneumonia, with the exclusion of SARS-CoV-2 pneumonia, the strength of the evidence does not support the safe and widespread use of corticosteroids as adjunctive therapy. Further studies are needed to identify subgroups of severe community-acquired pneumonia that can benefit or not from corticosteroids.
Reversing Transcriptome-Wide Association Studies to improve expression Quantitative Trait Loci associations
Authors: Yuan Jie , Lai Ben , Pe’er Itsik
Published: December 2020

1

Transcriptome-Wide Association Studies discover SNP effects mediated by gene expression through a two-stage process: a typically small reference panel is used to infer SNP-expression effects, and then these are applied to discover associations between imputed expression and phenotypes. We investigate whether the accuracy of SNP-expression and expression-phenotype associations can be increased by performing inference on both the reference panel and independent GWAS cohorts simultaneously. We develop EMBER (Estimation of Mediated Binary Effects in Regression) to re-estimate these effects using a liability threshold model with an adjustment to variance components accounting for imputed expression from GWAS data. In simulated data with only gene-mediated effects, EMBER more than doubles the performance of SNP-expression linear regression, increasing meanr2from 0.3 to 0.65 with a gene-mediated variance explained of 0.01. EMBER also improves estimation accuracy when the fraction of cis-SNP variance mediated by genes is as low as 30%. We apply EMBER to genotype and gene expression data in schizophrenia by combining 512 samples from the CommonMind Consortium and 56,081 samples from the Psychiatric Genomic Consortium. We evaluate performance of EMBER in 36 genes suggested by TWAS by concordance of inferred effects with effects reported independently for frontal cortex expression. Applying the EMBER framework to a baseline linear regression model increases performance in 26 out of 36 genes (sign test p-value .0020) with an increase in meanr2from 0.200 to 0.235.
Evaluation of exosome-encapsulated miR-23a/b in the diagnosis of human coronary heart diseases
Authors: Xu Changzhi , Xiao Hui , Yi Yanhua , Zhu Donglin , Yue Xiaojing , Xi Yun
Published: December 2020

Objective

Coronary heart disease (CHD) is currently one of the major causes of death with high morbidity. Due to the increasing heterogeneity and complexity in the CHDs progression, biomarkers for specific diagnosis and monitoring of disease progression need to be developed. The study was aimed to investigate the roles of serum exosomal miR-23a and miR-23b in diagnosis of CHDs.

Methods

16 healthy individuals and 56 patients with CHDs were enrolled in this study, including the CHDs of stable angina, unstable angina, non-ST elevation myocardial infarction (NSTEMI), ST elevation myocardial infarction (STEMI) and acute myocardial infarction (AMI). Serum exosomal miR-23a and miR-23b were quantified by Q-PCR. The associations of miR-23a/b with multiple clinical parameters were analyzed.

Results

Serum exosomal miR-23a was downregulated in the 56 CHD patients. In the specific prediction of stable angina and AMI, miR-23a achieved the area under the receiver operating characteristic (AUC-ROC) of 0.809 and 0.783, respectively. The levels of serum creatinine (CREA) and miR-23a were associated, which was consistent with risk of kidney injury in CHDs patients. Exosomal miR-23b levels showed no difference among CHD groups.

Conclusions

miR-23a may serve as a non-invasive marker in predicting stable angina and AMI. The level of miR-23a was implicated in CREA-dependent CHD-renal damage.
Coupling between ribotypic and phenotypic traits of protists across life-cycle stages and temperatures
Authors: Zou Songbao , Fu Rao , Deng Huiwen , Zhang Qianqian , Gentekaki Eleni , Gong Jun
Published: December 2020

Relationships between ribotypic and phenotypic traits of protists across life-cycle stages remain largely unknown. Herein, we used single cells of two soil and two marine ciliate species to examine phenotypic and ribotypic traits and their relationships across lag, log, plateau, cystic stages and temperatures. We found thatColpoda inflataandC. steiniidemonstrated allometric relationships between 18S rDNA copy number per cell (CNPC), cell volume (CV), and macronuclear volume across all life-cycle stages. Integrating previously reported data ofEuplotes vannusandStrombidium sulcatumindicated taxon-dependent rDNA CNPC–CV functions. Ciliate and prokaryote data analysis revealed that the rRNA CNPC followed a unified power-law function, only if the rRNA-deficient resting cysts were not considered. Hence, a theoretical framework was proposed to estimate the relative quantity of resting cysts in the protistan populations with total cellular rDNA and rRNA copy numbers. Using rDNA CNPC was a better predictor of growth rate at a given temperature than rRNA CNPC and CV, suggesting replication of redundant rDNA operons as a key factor that slows cell division. Single-cell high throughput sequencing and analysis after correcting sequencing errors revealed multiple rDNA and rRNA variants per cell. Both encystment and temperature affected the number of rDNA and rRNA variants in several cases. The divergence of rDNA and rRNA sequence in a single cell ranged from 1% to 10%, depending on species. These findings have important implications for inferring cell-based biological traits (e.g., species richness, abundance and biomass, activity, and community structure) of protists using molecular approaches.

Importance

Based on phenotypic traits, traditional surveys usually characterize organismal richness, abundance, biomass, and growth potential to describe diversity, organization and function of protistan populations and communities. The ribosomal RNA gene (rDNA) and its transcripts have been widely used as molecular markers in ecological studies of protists. Nevertheless, the manner in which these molecules relate to cellular (organismal) and physiological traits remains poorly understood, which could lead to misinterpretations of protistan diversity and ecology. The current research highlights the dynamic nature of cellular rDNA and rRNA contents, which tightly couple with multiple phenotypic traits in ciliated protists. We demonstrate that quantity of resting cysts and maximum growth rate of a population can be theoretically estimated using ribotypic trait-based models. The intra-individual sequence polymorphisms of rDNA and rRNA can be influenced by encystment and temperature, which should be considered when interpreting species-level diversity and community structure of microbial eukaryotes.
Design Principles of the ESCRT-III Vps24-Vps2 Module
Authors: Banjade Sudeep , Shah Yousuf H. , Tang Shaogeng , Emr Scott D.
Published: December 2020

ESCRT-III polymerization is required for all ESCRT-dependent events in the cell. However, the relative contributions of the eight ESCRT-III subunits differ between each process. The minimal features of ESCRT-III proteins necessary for function, and the role for the multiple ESCRT-III subunits remain unclear. To identify essential features of ESCRT-III subunits, we previously studied the polymerization mechanisms of two ESCRT-III subunits Snf7 and Vps24, identifying the association of the helix-4 region of Snf7 with the helix-1 region of Vps24 (Banjade et al., 2019). Here, we find that mutations in the helix-1 region of another ESCRT-III subunit Vps2 can functionally replace Vps24 inS. cerevisiae. Engineering and genetic selections revealed the required features of both subunits. Our data allow us to propose three minimal features required for ESCRT-III function – spiral formation, lateral association of the spirals through heteropolymerization, and binding to the AAA+ ATPase Vps4 for dynamic remodeling.
Structural basis for voltage-sensor trapping of the cardiac sodium channel by a deathstalker scorpion toxin
Authors: Jiang Daohua , Tonggu Lige , Gamal El-Din Tamer M. , Banh Richard , Pomès Régis , Zheng Ning , Catterall William A.
Published: December 2020

Voltage-gated sodium (NaV) channels initiate action potentials in excitable cells, and their function is altered by potent gating-modifier toxins. The α-toxin LqhIII from the deathstalker scorpion inhibits fast inactivation of cardiac NaV1.5 channels with IC50=11.4 nM. Here we reveal the structure of LqhIII bound to NaV1.5 at 3.3 Å resolution by cryo-EM. LqhIII anchors on top of voltage-sensing domain IV, wedged between the S1-S2 and S3-S4 linkers, which traps the gating charges of the S4 segment in a unique intermediate-activated state stabilized by four ion-pairs. This conformational change is propagated inward to weaken binding of the fast inactivation gate and favor opening the activation gate. However, these changes do not permit Na+permeation, revealing why LqhIII slows inactivation of NaV channels but does not open them. Our results provide important insights into the structural basis for gating-modifier toxin binding, voltage-sensor trapping, and fast inactivation of NaV channels.
Public value and the planet: accounting in ecological reconstitution
Authors: Vollmer Hendrik
Published: December 2020

Purpose

This paper explores the role of accounting in ecological reconstitution and draws attention to the public value as a topic of strategic interest for developing it.

Design/methodology/approach

The process of ecological reconstitution described by Latour in the “Politics of Nature” is traced towards a distinct set of accounting practices. These accounting practices, designated here as full-tax accounting, offer indications of the changing shape and role of accounting in ecological renewal.

Findings

Full-tax accounting extends the planetary public towards the inclusion of nonhuman planetarians. It establishes matters of care in multimodal accounts and haunts constitutional processes with the spectre of exclusion. Starting with full-tax accounting, public-value accountants emerge as curators of matters of care.

Research limitations/implications

The association of accounting in ecological reconstitution with matters of care highlights the mediating and immersive effects of accounting practice, inviting accounting scholars to explore these effects more systematically.

Practical implications

Accountants need to reconsider their stewardship role in relation to the fundamental uncertainties implied in planetary public-value accounting, support the process of ecological reconstitution by associating themselves with matters of care and develop ethics of exclusion.

Social implications

Broad alliances among planetary accountants are needed to extend the terms of ecological reconstitution, to gain and preserve attunement to matters of care and defend these attunements, in the atmospheric politics of ecological renewal, against regressive tendencies.

Originality/value

In problematising public value, the paper draws attention to a convergence of interests among scholars in accounting, public sector research and the environmental humanities. It presents a case for planetary accounting in ecological reconstitution that calls for participation from across disciplines, professions, arts and environmental activism.
The impact of COVID-19 on student motivation, community of inquiry and learning performance
Authors: Tan Consilz
Published: December 2020

Purpose

This paper aims to investigate the impact of COVID-19 on the students studying in higher education institutions pre and during Movement Control Order (MCO). MCO was introduced in March 2020, and the learning process must switch from face-to-face to online learning in schools and universities. This study particularly focuses on university students by analyzing the students' motivation, the community of inquiry and learning performance. In total, three factors are examined in the construct of the community of inquiry, namely social presence, cognitive presence and teaching presence.

Design/methodology/approach

This paper provides quantitative analysis and paired sample t-tests on the students' learning motivation, the community of inquiry and learning performance. This paper presents the analysis of the online learning preference of 282 university students and examines whether there is significant difference in preference before and during MCO.

Findings

The findings indicated that the students lost motivation and learning performance using online learning methods during the MCO period. There is a lack of infrastructure to support the learning and social support from the lecturers and peers.

Research limitations/implications

This research helps to explore improvements that are needed to manage such a pandemic to support teaching staff and students.

Practical implications

The COVID-19 is a pandemic that has affected the learning process of the students, and it should not be neglected even when it is over. Policymakers shall consider providing more training and better infrastructures to cater to smooth Internet connection and platform for online learning. Students are not able to focus on learning using online learning methods and, they lack motivation during the pandemic. The teaching faculty also need to be well-trained in delivering online courses and to be more tech-savvy.

Social implications

With the detailed analysis of the students' learning motivation, the community of inquiry and learning performance, it helps to promote a better education environment.

Originality/value

This is the first study to examine the learning motivation and performance model as well as the community of inquiry during the pandemic. It is evident that university students initially have a high level of motivation and community of inquiry before the pandemic but yield a significant drop during the MCO. The paper presented how COVID-19 seriously impacted on the learning experience.