bluuebunny/crossref_metadata_2025 huggingface dataset:
The Microstructural Record of Emplacement, Inflation and Convection of Sills, Lava Flows and Lakes
Authors: Holness Marian B , Neufeld Jerome
Published: October 2022

The stratigraphic variation of plagioclase grain shape in the marginal regions of tabular bodies of magma provides a record of the balance of heat loss into the surroundings and heat brought into the body by magma flow during inflation and propagation. This record has the potential to constrain the amount of magma flow past any point in a sill, enabling mapping the construction of any extensive sill network. The variation of plagioclase grain shape in lava lakes may preserve a detailed history of lake filling, whereas the history of inflation of a thick ponded flood basalt flow is likely to be lost by melt-back of any early formed chill during prolonged flow at the base. Convection sufficiently vigorous to entrain crystals from the marginal solidification fronts is recorded by stratigraphic invariance of plagioclase grain shape and is not generally found in sills: instead, plagioclase grain shape varies with stratigraphic height, attesting to a predominance of in situ plagioclase nucleation and growth at the intrusion margins. While the stratigraphic variation of plagioclase grain shape in sills thinner than ~100 m is symmetrical, that in thicker sills varies in an asymmetric way with stratigraphic height, suggestive of a slower rate of inwards propagation of the roof solidification front compared to the floor, most likely indicative of moderately vigorous convection. Sills are generally finer grained than dykes of the same thickness, regardless of whether the spatial variation of plagioclase shape is consistent with convection during solidification: this is likely to be a consequence of a greater extent of Ostwald ripening of suspended grains during long-lived convection in vertically extensive dykes.
Kelyphite Textures Experimentally Reproduced through Garnet Breakdown in the Presence of a Melt Phase
Authors: Ezad Isra S , Dobson David P , Thomson Andrew R , Jennings Eleanor S , Hunt Simon A , Brodholt John P
Published: October 2022

Complex multiphase reaction rims that form during garnet breakdown are known as kelyphite coronae and are common amongst exhumed mantle xenoliths. It has long been established that a reaction of garnet and olivine produces kelyphite corona consisting of spinel and pyroxenes, and that preservation of high-pressure garnet cores requires sufficiently rapid uplift of material through the spinel lherzolite stability field from depths of at least 60 km. We present new high-pressure, high-temperature experiments of garnet breakdown in the spinel–lherzolite stability field demonstrating that a series of cascading reactions can reproduce the multilayer, multiphase kelyphites seen in nature. In all experiments where breakdown occurred, a melt appears to have moderated the reactions towards equilibrium; we believe this to be the first experimental confirmation of the importance of such melts in garnet breakdown reactions. In our experiments at least three distinct zones of concentric kelyphite growth can occur at a single pressure, temperature condition; we suggest, therefore, that such kelyphites seen in natural samples do not have to be caused by a multistage uplift path as is often assumed. Kelyphitic coronae surrounding garnet have previously been used to estimate uplift rates; however, the lack of kinetic data for relevant exhumation reactions has limited their use for PTt pathway estimations and the understanding of emplacement mechanisms. In order to constrain accurate PTt pathways we use reaction rim thickness as a proxy for reaction progress and present preliminary results for the kinetics of garnet breakdown.
MYB30 and MYB14 form a repressor–activator module with WRKY8 that controls stilbene biosynthesis in grapevine
Authors: Mu Huayuan , Li Yang , Yuan Ling , Jiang Jinzhu , Wei Yongzan , Duan Wei , Fan Peige , Li Shaohua , Liang Zhenchang , Wang Lijun
Published: October 2022

When exposed to pathogen infection or ultraviolet (UV) radiation, grapevine (Vitis vinifera) plants rapidly accumulate the stilbenoid resveratrol (Res) with concomitant increase of stilbene synthase (STS), the key enzyme in stilbene biosynthesis. Although a few transcription factors have been shown to regulate STSs, the molecular mechanism governing the regulation of STSs is not well elucidated. Our previous work showed that a VvMYB14–VvWRKY8 regulatory loop fine-tunes stilbene biosynthesis in grapevine through protein–protein interaction; overexpression of VvWRKY8 down-regulates VvMYB14 and VvSTS15/21; and application of exogenous Res up-regulates WRKY8 expression. Here, we identified an R2R3-MYB repressor, VvMYB30, which competes with the activator VvMYB14 for binding to the common binding sites in the VvSTS15/21 promoter. Similar to VvMYB14, VvMYB30 physically interacts with VvWRKY8 through their N-termini, forming a complex that does not bind DNA. Exposure to UV-B/C stress induces VvMYB14, VvWRKY8, and VvSTS15/21, but represses VvMYB30 in grapevine leaves. In addition, MYB30 expression is up-regulated by VvWRKY8-overexpression or exogenous Res. These findings suggest that the VvMYB14–VvWRKY8–VvMYB30 regulatory circuit allows grapevine to respond to UV stress by producing Res and prevents over-accumulation of Res to balance metabolic costs. Our work highlights the stress-mediated induction and feedback inhibition of stilbene biosynthesis through a complex regulatory network involving multiple positive and negative transcriptional regulators.
Differential network analysis of oral microbiome metatranscriptomes identifies community scale metabolic restructuring in dental caries
Authors: Espinoza Josh L , Torralba Manolito , Leong Pamela , Saffery Richard , Bockmann Michelle , Kuelbs Claire , Singh Suren , Hughes Toby , Craig Jeffrey M , Nelson Karen E , Dupont Chris L
Published: October 2022

Dental caries is a microbial disease and the most common chronic health condition, affecting nearly 3.5 billion people worldwide. In this study, we used a multiomics approach to characterize the supragingival plaque microbiome of 91 Australian children, generating 658 bacterial and 189 viral metagenome-assembled genomes with transcriptional profiling and gene-expression network analysis. We developed a reproducible pipeline for clustering sample-specific genomes to integrate metagenomics and metatranscriptomics analyses regardless of biosample overlap. We introduce novel feature engineering and compositionally-aware ensemble network frameworks while demonstrating their utility for investigating regime shifts associated with caries dysbiosis. These methods can be applied when differential abundance modeling does not capture statistical enrichments or the results from such analysis are not adequate for providing deeper insight into disease. We identified which organisms and metabolic pathways were central in a coexpression network as well as how these networks were rewired between caries and caries-free phenotypes. Our findings provide evidence of a core bacterial microbiome that was transcriptionally active in the supragingival plaque of all participants regardless of phenotype, but also show highly diagnostic changes in the ways that organisms interact. Specifically, many organisms exhibit high connectedness with central carbon metabolism to Cardiobacterium and this shift serves a bridge between phenotypes. Our evidence supports the hypothesis that caries is a multifactorial ecological disease.
Optic nerve sheath diameter, intensive care unit admission and COVID-19-related-in-hospital mortality
Authors: Gültekin H , Güven M
Published: October 2022

Background

Hypoxia and hypercapnia due to acute pulmonary failure in patients with coronavirus disease 2019 (COVID-19) can increase the intracranial pressure (ICP). ICP correlated with the optic nerve sheath diameter (ONSD) on ultrasonography and is associated with a poor prognosis.

Aim

We investigated the capability of ONSD measured during admission to the intensive care unit (ICU) in patients with critical COVID-19 in predicting in-hospital mortality.

Methods

A total of 91 patients enrolled in the study were divided into two groups: survivor (n = 48) and nonsurvivor (n = 43) groups. ONSD was measured by ultrasonography within the first 3 h of ICU admission.

Results

The median ONSD was higher in the nonsurvivor group than in the survivor group (5.95 mm vs. 4.15 mm, P < 0.001). The multivariate Cox proportional hazard regression analysis between ONSD and in-hospital mortality (contains 26 covariates) was significant (adjusted hazard ratio, 4.12; 95% confidence interval, 1.46–11.55; P = 0.007). The ONSD cutoff for predicting mortality during ICU admission was 5 mm (area under the curve, 0.985; sensitivity, 98%; and specificity, 90%). The median survival of patients with ONSD >5 mm (43%; n = 39) was lower than those with ONSD ≤5 mm (57%; n = 52) (11.5 days vs. 13.2 days; log-rank test P = 0.001).

Conclusions

ONSD ultrasonography during ICU admission may be an important, cheap and easy-to-apply method that can be used to predict mortality in the early period in patients with critical COVID-19.
Building and Landing the Plane While Flying: How New York State Addressed the Needs of People With Serious Mental Illness During the COVID-19 Pandemic
Authors: Erlich Matthew D , Casoy Flavio , Berezin Joshua , Hernandez Yamilette , Smith Thomas E
Published: October 2022

New York State was the epicenter for COVID-19 in Spring 2020 when little was known about the pandemic. Dire circumstances necessitated New York State’s (NYS) public mental health system to rapidly pivot, adapt, and innovate its policies and procedures to ensure continuous high-level care to individuals with serious mental illness (SMI), a population especially vulnerable to both the physical and psychosocial sequelae of COVID-19. NYS rapidly adopted emergency measures to support community providers, expanded the capacity of its State-Operated facilities, created policies to promote improved infection control access, collaborated to enhance the public–private continuum of service to support people with SMI, and broadened the use of new technologies to ensure continued engagement of care.
How Did the Mental Health Care System in India Respond to COVID 19 Pandemic?
Authors: Rangaswamy Thara , Grover Sandeep , Tyagi Vidhi , Bhan Anant
Published: October 2022

India with a population of 1.3 billion has a unique health care system in its different states. Mental health care varies widely across the country and this became even more apparent after the COVID-19 pandemic set in. This paper examines the various strategies in response to COVID-19 adopted by the Government of India, the health departments of the individual states, and other private players such as on-government organizations and the civil society. The cessation of many services including outpatient and inpatient care and the scarcity of medicines were serious impacts of COVID-19. The prolonged lockdown in many parts of the country impeded access to mental health care services since public transport was unavailable. This led to many relapses in persons with serious mental disorders. The emergence of new cases of psychosis and an increase in suicides were also seen. Tele consultations came to the fore and many helplines were started offering counseling and guidance regarding the availability of mental health care facilities. While these helped the urban dwellers, those in remote and rural areas were unable to use these services effectively. Many mental health wards were used for COVID-19 patients and mental health professionals were deployed for COVID-19 related duty. The severely mentally ill, the homeless mentally ill, and the elderly were especially vulnerable. Based on our experience with COVID-19, we urge a strong call for action, in terms of strengthening the primary care facilities and increasing the manpower resources to deliver mental health care.
Diglossia Correlates With Prodromal Symptoms of Psychosis Among First-Generation Migrants
Authors: Alherz Mohammad , Almusawi Hashemiah , Alsayegh Ammar
Published: October 2022

Background and Hypothesis

We have previously hypothesized that diglossia may be a risk factor for psychosis, drawing from observations on migration, ethnicity, social adversity, and language disturbances among others. However, empirical data on this association and the tools necessary for its measurement are limited.

Study Design

In a cross-sectional online sample of first-generation migrants residing in majority English-speaking countries, a response-based decision tree was introduced to classify the sociolinguistic profiles of 1497 participants as either with or without diglossia. Using multivariate logistic regression, the association of diglossia with psychosis risk screening outcomes in the Prodromal Questionnaire-16 was calculated, adjusting for demographic and linguistic confounders. Differences in the symptom categories endorsed between the 2 groups were also examined.

Study Results

Diglossia was identified in 18.4% of participants and was associated with an adjusted odds ratio of 2.58 for a positive risk screening outcome. Other significant factors included subjective social status, hearing difficulty, age, sex, country of residence, education level, and cannabis consumption. The effects of ethnicity, age at migration, fluency, relationship, and employment status were no more significant in the multivariate model. Finally, the largest differences in the proportion of positively responding participants between the two groups were found in symptoms relating to thought insertion and thought broadcasting.

Conclusions

In a sociolinguistic hierarchical framework, diglossia is correlated with prodromal symptoms of psychosis in first-generation migrants.
The dynamics of policy coordination: The case of China’s science and technology policy-making
Authors: Huang Ying , Li Yashan , Mao Jinge , Li Ruinan , Zhang Lin
Published: October 2022

The literature on policy coordination between government agencies reveals little about how coordination is managed in centralized political systems. This paper, therefore, presents a dynamic and quantitative analysis of policy coordination in China based on the science and technology (S&T) policy documents issued by China’s central government agencies in the period 1978–2019. From a series of snapshots depicting inter-agency policy development in five historical stages over this timeframe, we find that (1) policy coordination has developed steadily and has mainly occurred to interpret macro strategies and put in place more detailed implementation measures. (2) Ministries under the purview of the State Council have played a leading role in policy coordination, while other types of agencies have cooperated in more supporting roles. (3) Coordination efforts have mainly focused on inclusive and national demand-oriented themes, such as high-tech industrialization, rural S&T, and social development. This research offers a panoramic view of policy coordination trajectories and mechanisms in centralized political systems. As such, it adds to the analysis methods available for quantitatively studying policy documents.
A Robust Disease Scoring Method to ScreenEucalyptusfor Resistance Against the Aggressive Leaf PathogenTeratosphaeria destructans
Authors: Solís Myriam , Hammerbacher Almuth , Wingfield Michael J. , Naidoo Sanushka
Published: October 2022

Shoot and leaf blight caused by Teratosphaeria destructans is one of the most devastating foliar diseases on Eucalyptus. Therefore, breeding for resistance to this disease is considered urgent. Differences in susceptibility to T. destructans have been observed in the field but a robust inoculation protocol has, until recently, been unavailable and a disease scoring method for precise phenotyping has not been established. A first objective of this study was to determine the optimal conidial concentration for T. destructans inoculations on a susceptible Eucalyptus host. This concentration was then used to determine differences in susceptibility of six genotypes of Eucalyptus grandis × E. urophylla to the pathogen by assessing the percentage of infected stomata using electron microscopy and the percentage of leaf area covered by lesions (PLACL) using image processing. In addition, we developed a disease susceptibility index (SI) of six categories ranging from highly resistant (SI = 0) to highly susceptible (SI = 1.5 to 2). The more resistant genotypes were moderately resistant, with an SI value of 0.49 to 0.54 and a PLACL of 6.5 to 9%. In contrast, the more susceptible genotype scored an SI of 1.52 and PLACL of 48%. Host susceptibility was also assessed relative to the sporulation of the pathogen. This showed that the percentage of sporulation was not significantly correlated with host resistance. Overall, the results provide the basis for rigorous screening and selection of resistant genotypes to the disease caused by T. destructans using artificial inoculation.
Patterns of Substance Use During Early Pregnancy and Associations With Behavioral Health Characteristics
Authors: Sujan Ayesha C. , Alexeeff Stacey E. , Slama Natalie , Avalos Lyndsay A. , Adams Sara R. , Conway Amy , Ansley Deborah , Young-Wolff Kelly C.
Published: October 2022

Objectives

The aims of the study are to identify patterns of early pregnancy substance use and to examine how these patterns relate to behavioral health conditions measured in early pregnancy.

Methods

We conducted a retrospective observational study (N= 265,274 pregnancies) screened for alcohol, cannabis, nicotine, pharmaceutical opioids, and stimulants during the first trimester via self-report and urine toxicology tests in Kaiser Permanente Northern California from January 1, 2012, to December 31, 2019. To identify patterns of prenatal substance use, we conducted latent class analysis. We then calculated the prevalence of depression, anxiety, intimate partner violence, and family drug use history for each prenatal substance use group and compared the prevalences by estimating prevalence ratios using modified Poisson regression, adjusting for sociodemographic characteristics.

Results

We identified the following 4 latent groups with different patterns of substance use: (a) predominantly alcohol and no other substances (9.30%), (b) predominantly cannabis and no other substances (4.88%), (c) predominantly nicotine and some pharmaceutical opioids (1.09%), and (d) high-polysubstance (alcohol, cannabis, nicotine, and stimulants; 0.36%); these pregnancies were compared with (e) no prenatal substance use (84.37%). The prevalence of all behavioral health conditions was elevated in all prenatal substance use groups compared with the no substance use group. Furthermore, the prevalence of depressive and anxiety disorders, intimate partner violence and family drug use history were greater in the high-polysubstance cluster than the alcohol and cannabis clusters.

Conclusions

Results highlight the importance of screening and interventions for all types of substance use during early pregnancy and suggest a particularly high need to prioritize targeting early interventions to pregnant and reproductive age individuals with polysubstance use.
Struggling With Recovery From Opioids: Who Is at Risk During COVID-19?
Authors: Keith Diana R. , Tegge Allison N. , Stein Jeffrey S. , Athamneh Liqa N. , Craft William H. , Chilcoat Howard D. , Le Moigne Anne , DeVeaugh-Geiss Angela , Bickel Warren K.
Published: October 2022

Objectives

Individuals in recovery from opioid use disorder (OUD) are vulnerable to the impacts of the COVID-19 pandemic. Recent findings suggest increased relapse risk and overdose linked to COVID-19–related stressors. We aimed to identify individual-level factors associated with COVID-19–related impacts on recovery.

Methods

This observational study (NCT04577144) enrolled 216 participants who previously partook in long-acting buprenorphine subcutaneous injection clinical trials (2015–2017) for OUD. Participants indicated how COVID-19 affected their recovery from substance use. A machine learning approach Classification and Regression Tree analysis examined the association of 28 variables with the impact of COVID-19 on recovery, including demographics, substance use, and psychosocial factors. Ten-fold cross-validation was used to minimize overfitting.

Results

Twenty-six percent of the sample reported that COVID-19 had made recovery somewhat or much harder. Past-month opioid use was higher among those who reported that recovery was harder compared with those who did not (51% vs 24%, respectively; P < 0.001). The final classification tree (overall accuracy, 80%) identified the Beck Depression Inventory (BDI-II) as the strongest independent risk factor associated with reporting COVID-19 impact. Individuals with a BDI-II score ≥10 had 6.45 times greater odds of negative impact (95% confidence interval, 3.29–13.30) relative to those who scored <10. Among individuals with higher BDI-II scores, less progress in managing substance use and treatment of OUD within the past 2 to 3 years were also associated with negative impacts.

Conclusions

These findings underscore the importance of monitoring depressive symptoms and perceived progress in managing substance use among those in recovery from OUD, particularly during large-magnitude crises.
Factors Associated With Severe Bacterial Infections in People Who Inject Drugs: A Single-center Observational Study
Authors: Hrycko Alexander , Mateu-Gelabert Pedro , Ciervo Courtney , Linn-Walton Rebecca , Eckhardt Benjamin
Published: October 2022

Background

People who inject drugs are at increased risk for several bacterial infections such as bacteremia, endocarditis, and osteomyelitis resulting in severe morbidity and high care costs. Limited data exist surrounding the injection drug use practices and behaviors that may increase the risk of these infections.

Methods

Individuals admitted to a single hospital in New York City with severe bacterial infection, between August 2020 and June 2021, were recruited to partake in an in-depth survey examining potential factors, both demographic and injection drug use behavioral, associated with severe bacterial infections.

Results

Thirty-four participants were recruited with injection drug use–associated severe bacterial infection. The mean age was 36.5 years; 21 (62%) were currently homeless, with 19 (56%) patients admitted for infective endocarditis. The mean length of hospital stay of all participants was 32.2 days; 94% received medication for opioid use disorder while admitted, whereas 35% left before treatment completion with a patient-directed discharge or elopement. Eight-two percent of participants were injected daily in the prior 30 days, with an average of 276 injections per participant. Fifty percent of participants reported requiring multiple sticks per injection event “always” or “very often,” with 94% reporting reuse of syringes in the prior month.

Conclusions

Severe bacterial infections in people who inject drugs resulted in prolonged and complex hospitalization that culminate in suboptimal outcomes despite aggressive measures to engage patients in medication for opioid use disorder. Numerous nonsterile injection drug use practices were identified, indicating a gap in current infection prevention harm reduction messaging.
Relationship Between Tinnitus and Hearing Outcomes Among US Military Personnel After Blast Injury
Authors: Myers Emily E. , Joseph Antony R. , Dougherty Amber L. , Clouser Mary C. , MacGregor Andrew J.
Published: October 2022

Objectives:

To examine the association between tinnitus and hearing outcomes among US military personnel after blast injury, including any hearing loss, low-frequency hearing loss, high-frequency hearing loss, early warning shift, and significant threshold shift.

Design:

In this retrospective study, the Blast-Related Auditory Injury Database was queried for male military service members who had audiometric data 2 years before and after blast injury between 2004 and 2012 with no history of hearing loss or tinnitus before injury (n = 1693). Tinnitus was defined by diagnostic codes in electronic health records. Multivariable logistic regression examined the association between tinnitus and hearing outcomes, while adjusting for covariates.

Results:

Overall, 14.2% (n = 241) of the study sample was diagnosed with tinnitus within 2 years after blast injury. The proportions of all examined hearing outcomes were higher among service members with tinnitus than those without (p < 0.001). In multivariable analysis, service members with tinnitus had higher adjusted odds of any hearing loss (odds ratio [OR] = 1.72, 95% confidence interval [CI] = 1.20–2.47), low-frequency hearing loss (OR = 2.77, 95% CI = 1.80–4.26), high-frequency hearing loss (OR = 2.15, 95% CI = 1.47–3.16), early warning shift (OR = 1.83, 95% CI = 1.36–2.45), and significant threshold shift (OR = 2.15, 95% CI = 1.60–2.89) compared with service members without tinnitus.

Conclusions:

The findings of this study demonstrate that tinnitus diagnosed within 2 years after blast injury is associated with the examined hearing outcomes in US military personnel. Service members with blast injury who subsequently experience tinnitus should receive routine audiometric hearing conservation testing and be carefully examined for poor hearing outcomes by an audiologist.
Insights into the pathogenic role of neutrophils in systemic lupus erythematosus
Authors: Ma Shiliang , Jiang Wanlan , Zhang Xuan , Liu Wei
Published: October 2022

Purpose of review

Although dysregulated adaptive immune response has been considered as the main culprit for systemic lupus erythematosus (SLE), emerging studies have indicated that innate immunity, functioning upstream of adaptive immunity, acts as an important trigger of autoimmune diseases and promotes SLE development. Here, we have reviewed the most recent findings to highlight the influence of neutrophils on SLE pathogenesis.

Recent findings

Neutrophils participate in SLE development mainly via promoting self-antigen exposure and autoantibody production, advocating the release of type I interferons (IFNs) and other pro-inflammatory cytokines, and mediating systemic tissue injury. A recent study revealed that neutrophil ferroptosis exerts a strong pathogenic effect in SLE, and that dysregulated innate immunity is adequate to disrupt the homeostasis of immune tolerance.

Insights into the pathogenic role of neutrophils in SLE will contribute to a more comprehensive understanding of this disease and may propose novel clinical targets for accurate diagnosis and precision medicine.
Preoperative Association Between Quantitative Lumbar Muscle Parameters and Spinal Sagittal Alignment in Lumbar Fusion Patients
Authors: Moser Manuel , Okano Ichiro , Albertini Sanchez Leonardo , Salzmann Stephan N. , Carlson Brandon B. , Adl Amini Dominik , Oezel Lisa , Chiapparelli Erika , Tan Ek T. , Shue Jennifer , Sama Andrew A. , Cammisa Frank P. , Girardi Federico P. , Hughes Alexander P.
Published: October 2022

Study Design.

A retrospective cross-sectional study.

Objective.

To assess the association between spinal muscle morphology and spinopelvic parameters in lumbar fusion patients, with a special emphasis on lumbar lordosis (LL).

Summary of Background Data.

Maintenance of sagittal alignment relies on muscle forces, but the basic association between spinal muscles and spinopelvic parameters is poorly understood.

Materials and Methods.

Patients operated between 2014 and 2017 who had both lumbar magnetic resonance imaging scan and standing whole-spine radiographs within six months before surgery were included. Muscle measurements were conducted on axial T2-weighted magnetic resonance images at the superior endplate L3–L5 for the psoas and L3–S1 for combined multifidus and erector spinae (paraspinal) muscles. A pixel intensity threshold method was used to calculate the total cross-sectional area (TCSA) and the functional cross-sectional area (FCSA). Spinopelvic parameters were measured on lateral standing whole-spine radiographs and included LL, pelvic incidence (PI), PI-LL mismatch, pelvic tilt, sacral slope, thoracic kyphosis, and sagittal vertical axis. Analyses were stratified by biological sex. Multivariable linear regression analyses with adjustments for age and body mass index (BMI) were performed.

Results.

A total of 104 patients (62.5% female) were included in the analysis. The patient population was 90.4% White with a median age at surgery of 69 years and a median BMI of 27.8 kg/m2. All muscle measurements were significantly smaller in women. PI, pelvic tilt, and thoracic kyphosis were significantly greater in women. PI-LL mismatch was 6.1° (10.6°) in men and 10.2° (13.5°) in women (P=0.106), and sagittal vertical axis was 45.3 (40.8) mm in men and 35.7 (40.8) mm in women (P=0.251). After adjusting for age and BMI, paraspinal TCSA at L3–L5, and paraspinal FCSA at L4 showed significant positive associations with LL in women. In men, psoas TCSA at L5 and psoas FCSA at L5 showed significant negative associations with LL, but none of the paraspinal muscle measurements.

Conclusion.

Our findings indicate that psoas and lumbar spine extensor muscles interact differently on LL among men and women, creating a unique mechanical environment.

Level of Evidence.

Level 4.
Factors Affecting the Accuracy of Pedicle Screw Placement in Robot-Assisted Surgery: A Multi-Center Study
Authors: Toossi Nader , Vardiman Arnold B. , Benech Carlo A. , Kanaly Charles W. , Maltenfort Mitchell G. , Backes Danielle M. , Bucklen Brandon
Published: October 2022

Study Design.

Retrospective Multi-Center

Objective.

To investigate the factors involved in, and their relative contributions to, the overall accuracy of robot-assisted pedicle screw placement

Summary of Background Data.

Robot-assisted surgery has reportedly resulted in greater accuracy for placement of pedicle screws than conventional methods. There are many potential factors affecting the accuracy of pedicle screws placed with a robot. No study has investigated these factors in a robust way.

Methods.

Radiographic and clinical data of three centers were pooled. Pre- and post-operative computerized tomographies were obtained by all three centers to assess the accuracy of the placed screws. The primary outcome measured was accuracy of pedicle screws placed with the robot. The authors performed a multivariate regression analysis to determine the significant patient- and screw-related variables and their relative contribution to the overall accuracy. In addition, an ordinal regression analysis was conducted to investigate the effects of different variables on accuracy of robot-placed screws graded by Gertzbein-Robbins grading system (GRS).

Results.

The total contribution of all studied variables to overall accuracy variation as measured by offsets between the placed and planned screws was only 18%. Obesity, long constructs, female gender, surgeon, and vertebral levels were among the factors that had small contributions to the different screw offsets. For GRS grades, significant variables were gender (Log odds:0.62, 95% CI: 0.38-0.85), age (Log odds: 0.02, 95% CI: 0.01-0.03), length of constructs (Log odds: 0.07, 95% CI: 0.02-0.11), screw diameter (Log odds: 0.55, 95% CI: 0.39-0.71), and length of the screws (Log odds: 0.03, 95% CI: 0.01-0.05). However, these variables too, regardless of their significant association with the accuracy of placed screws, had little contribution to overall variability of accuracy itself (only about 7%).

Conclusion.

The accuracy of screws placed with robotic assistance, as graded by GRS or measured offsets between planned and placed screw trajectories, is minimally affected by different patient- or screw-related variables due to the robustness of the robotic navigation system used in this study.
The Impact of the COVID-19 Pandemic on the Presentation of Patients With Spinal Metastases
Authors: Mika Aleksander P. , Wollenman Colby , Steinle Anthony M. , Chanbour Hani , Vaughan Wilson , Croft Andrew , Lugo-Pico Julian , Zuckerman Scott L. , Abtahi Amir M. , Stephens Byron F.
Published: October 2022

Study Design.

Retrospective review.

Objective.

The aim was to determine if preoperative spinal instability neoplastic scores (SINSs) and Tokuhashi prognostication scores differed in patients receiving surgical care before and during the coronavirus disease-2019 (COVID-19) pandemic.

Summary of Background Data.

The COVID-19 pandemic has caused delays in scheduling nonemergent surgeries. Delay in presentation and/or surgical treatment for oncology patients with metastatic spinal disease could result in progression of the disease, which can complicate surgical care and worsen patient outcomes.

Materials and Methods.

Retrospective review of electronic medical records between March 1, 2019 and March 1, 2021 at a tertiary medical center was performed to identify patients who underwent surgery for metastatic spine disease. Primary spinal tumors were excluded. Patients were separated into two groups base on their surgery date: before the COVID-19 pandemic (March 1, 2019–February 29, 2020) and during the COVID-19 pandemic (March 1, 2020–March 1, 2021). Primary outcomes included SINS and Tokuhashi scores. A variety of statistical tests were performed to compare the groups.

Results.

Fifty-two patients who underwent surgery before the COVID-19 pandemic were compared to 41 patients who underwent surgery during the COVID-19 pandemic. There was a significant difference between the before and during groups with respect to SINS (9.31±2.39 vs. 11.00±2.74, P=0.002) and Tokuhashi scores (9.27±2.35 vs. 7.88±2.85, P=0.012). Linear regression demonstrated time of surgery (before or during COVID-19 restrictions) was a significant predictor of SINS (β=1.55, 95% CI: 0.42–2.62, P=0.005) and Tokuhashi scores (β=−1.41, 95% CI: −2.49 to −0.34, P=0.010).

Conclusions.

Patients with metastatic spinal disease who underwent surgery during the COVID-19 pandemic had higher SINS, lower Tokuhashi scores and similar Skeletal Oncology Research Group scores compared to patients who underwent surgery before the pandemic. This suggests the pandemic has impacted the instability of disease at presentation in patients with spinal metastases, but has not impacted surgical prognosis, as there were no differences in Skeletal Oncology Research Group scores and the difference in Tokuhashi scores is most likely not clinically significant.
Propensity-matched Comparison Between Chronic Nonspecific Low Back Pain and Axial Spondyloarthritis: Impact on patient-perceived Quality of Life
Authors: Cheung Jason Pui Yin , Cheung Prudence Wing Hang , Wong Carlos King Ho , Chung Ho Yin , Tsang Helen Hoi Lun
Published: October 2022

Study Design.

Prospective study.

Objective.

To compare the burden between chronic nonspecific low back pain (LBP) and axial spondyloarthropathy (SpA).

Summary of Background Data.

Chronic nonspecific LBP and SpA are two debilitating yet different chronic musculoskeletal disorders. To compare their burden, propensity score matching is used to control for potential confounders and match the study subjects.

Materials and Methods.

Two prospectively collected cohorts of LBP (n=269) and SpA (n=218) patients were studied. Outcomes included current LBP, 36-item Short Form Questionnaire, Oswestry Disability Index, EuroQol 5-dimension 5-level Questionnaire, and EuroQol Visual Analog Scale. With the inherent differences between the two types of patients, propensity score matching was performed for comparing the two groups. Baseline covariates of age, sex, education level, occupation, smoking, and drinking history were selected for the estimation of propensity scores for each subject with the logistic regression model. Significant independent variables for the outcome of current back pain were included in the multivariate logistic regressions.

Results.

A total of 127 matched pairs were identified, with 254 patients. In the matched cohort, more patients with chronic LBP had current back pain (95.3%) as compared with SpA (71.7%). Patients with SpA were younger (P<0.001), with more males (P<0.001), and better educated (P=0.001). There was less current back pain and higher nonsteroidal anti-inflammatory drug use (P<0.001). Most SpA patients had lower Oswestry Disability Index than LBP patients and with low disease activity. Patients with LBP had worse outcome scores as compared with SpA patients given the same Visual Analog Scale. LBP patients had 8.6 times the odds (95% CI: 3.341–20.671; P<0.001) of experiencing current back pain compared with SpA patients.

Conclusions.

The disease activity of SpA patients is well controlled. However, patients with chronic LBP have worse pain severity, disability, and health-related quality of life. This has implications on resource utilization and the necessity of advancing LBP understanding and management.

Level of Evidence.

Type I prognostic study.
Circ_0003998 upregulates ARK5 expression to elevate 5-Fluorouracil resistance in hepatocellular carcinoma through binding to miR-513a-5p
Authors: Xue Liang , He Jiefeng , Chen Haiyun , Ren Chongren , Fu Xifeng
Published: October 2022

Chemoresistance has limited clinical treatment of cancer patients. This study aimed to research the regulatory function of circ_0003998 in 5-Fluorouracil (5-FU) resistance. Circ_0003998, microRNA-513a-5p (miR-513a-5p) and AMPK-Related Protein Kinase 5 (ARK5) levels were assayed via the quantitative reverse transcription-PCR. Colony formation ability was assessed by colony formation assay. Flow cytometry was performed for cell cycle and cell apoptosis analysis. Caspase-3 activity was detected using a caspase-3 activity assay. Target analysis was conducted via RNA pull-down assay, a dual-luciferase reporter assay, and an RNA immunoprecipitation assay. In-vivo assay was performed by establishing a xenograft model in mice. Circ_0003998 was upregulated in 5-FU-resistant hepatocellular carcinoma (HCC) tissues and cells. Circ_0003998 downregulation repressed 5-FU resistance and cancer progression in 5-FU-resistant HCC cells. Circ_0003998 interacted with miR-513a-5p. Inhibition of miR-513a-5p reversed the regulation of sh-circ_0003998 in 5-FU resistance. ARK5 was a target of miR-513a-5p, and ARK5 was regulated by circ_0003998 via targeting miR-513a-5p. Circ_0003998 regulated 5-FU resistance partly by upregulating ARK5 expression. 5-FU sensitivity was enhanced after circ_0003998 level reductionin vivo. These findings unraveled that circ_0003998 elevated 5-FU resistance in HCC by sponging miR-513a-5p to upregulate the level of ARK5, indicating that circ_0003998 might be used as a target to improve 5-FU therapy for HCC.
The Association of Immunotherapy With the Overall Survival of Inoperable Stage III Non-small Cell Lung Cancer Patients Who Do Not Receive Chemoradiation
Authors: Amin Saber A. , Baine Michael J. , Rahman Ibur , Lin Chi
Published: October 2022

Immunotherapy has been approved for stage III non-small cell lung cancer (NSCLC) as consolidation therapy after chemoradiation in patients whose disease does not progress after chemoradiation. However, many patients do not receive chemoradiation due to either the drugs’ side effects or poor performance status. This study’s objective is to investigate the association of immunotherapy combined with chemotherapy or Radiotherapy (RT) with the overall survival (OS) of stage III NSCLC patients who do not receive chemoradiation. Patients with stage III NSCLC who received either chemotherapy or RT with or without immunotherapy were identified from NCDB. The Cox proportional hazard regression analysis was implied to assess the effect of immunotherapy on survival after adjusting the model for age at diagnosis, race, sex, education, treatment facility type, insurance status, comorbidity score, histology year of diagnosis, and treatment types, such as chemotherapy and radiation therapy. The final analysis included 32,328 patients, among whom 3,205 (9.9%) received immunotherapy. In the multivariable analysis adjusted for all the factors previously mentioned, immunotherapy was associated with significantly improved OS (HR: 0.76, CI: 0.71–0.81) compared with no immunotherapy. Treatment with chemotherapy plus immunotherapy was significantly associated with improved OS (HR: 0.83, CI: 0.77–0.90) compared with chemotherapy without immunotherapy. Further, RT plus immunotherapy was associated with significantly improved OS (HR: 0.62, CI: 0.54–0.70) compared with RT alone. In this comprehensive analysis, the addition of immunotherapy to chemotherapy or radiotherapy was associated with improved OS compared with chemotherapy or radiation therapy without immunotherapy in stage III NSCLC patients.
Prevalence and prognostic impact of hepatopulmonary syndrome in patients with unresectable hepatocellular carcinoma undergoing transarterial chemoembolization: a prospective cohort study
Authors: Zhao He , Tsauo Jiaywei , Zhang Xiaowu , Ma Huaiyuan , Weng Ningna , Yang Zhengqiang , Li Xiao
Published: October 2022

Background:

To determine the prevalence and prognostic impact of hepatopulmonary syndrome (HPS) in patients with unresectable hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE).

Methods:

Fifty-four patients with unresectable HCC undergoing TACE between December 2014 and December 2015 were prospectively screened for HPS and were followed up for a maximum of 2 years or until the end of this prospective study.

Results:

Nineteen of the 54 (35.2%) patients were considered to have HPS, including one (5.3%) with severe HPS, nine (47.4%) with moderate HPS, and nine (47.4%) with mild HPS. The median overall survival (OS) was 10.1 (95% confidence interval [CI], 3.9–16.3) months for patients with HPS and 15.1 (95% CI, 7.3–22.9) months for patients without HPS, which is not a significant difference (P = 0.100). The median progression-free survival was also not significantly different between patients with and without HPS (5.2 [95% CI, 0–12.8] vs. 8.4 [95% CI, 3.6–13.1] months; P = 0.537). In the multivariable Cox regression analyses, carbon monoxide diffusing capacity (hazard ratio [HR] = 1.033 [95% CI, 1.003–1.064]; P = 0.028) and Child-Pugh class (HR = 1.815 [95% CI, 1.011–3.260]; P = 0.046) were identified to be the independent prognostic factors of OS.

Conclusion:

Mild or moderate HPS is common in patients with unresectable HCC undergoing TACE, but it does not seem to have a significant prognostic impact.
Ferroptosis and its emerging roles in acute pancreatitis
Authors: Li Hongyao , Lin Yujie , Zhang Ling , Zhao Jing , Li Peiwu
Published: October 2022

Acute pancreatitis (AP) is a common and potentially life-threatening pancreatic inflammatory disease. Although it is usually self-limiting, up to 20% of patients will develop into severe AP. It may lead to systemic inflammatory response syndrome and multiple organ dysfunction, affecting the lungs, kidneys, liver, heart, etc. Surviving patients usually have sequelae of varying degrees, such as chronic hyperglycemia after AP (CHAP), pancreatic exocrine insufficiency, and chronic pancreatitis. Lacking specific target treatments is the main reason for high mortality and morbidity, which means that more research on the pathogenesis of AP is needed. Ferroptosis is a newly discovered regulated cell death (RCD), originally described in cancer cells, involving the accumulation of iron and the depletion of plasma membrane polyunsaturated fatty acids, and a caspase-independent RCD. It is closely related to neurological diseases, myocardial infarction, ischemia/reperfusion injury, cancer, etc. Research in the past years has also found the effects of ferroptosis in AP, pancreatic cancer, and AP complications, such as acute lung injury and acute kidney injury. This article reviews the research progress of ferroptosis and its association with the pathophysiological mechanisms of AP, trying to provide new insight into the pathogenesis and treatment of AP, facilitating the development of better-targeted drugs.
The Umbilical Cord and Complications of Twin Gestations
Authors: Van Grambezen Aurianne , Steenhaut Patricia , Van Grambezen Bénédicte , Debiève Frédéric , Bernard Pierre , Hubinont Corinne
Published: October 2022

The rate of twin pregnancies has increased over the last decades, largely because of the ongoing development of assisted reproductive technology and increased maternal age at childbearing. Twins have a higher risk of adverse outcomes during pregnancy and the perinatal period. The prevalence of umbilical cord abnormalities is higher for twin pregnancies compared with singleton pregnancies. Some of these abnormalities are nonspecific to twinning and can also be found in singleton gestations (such as velamentous cord insertion, vasa previa, and single umbilical artery). Other abnormalities are associated with monochorionic twins, such as umbilical cord entanglement, and umbilical proximate cord insertion. Most of these abnormalities can be detected by ultrasound evaluation. The early and accurate ultrasound diagnosis of chorionicity, amnionicity, and placental and umbilical cord characteristics is crucial if we are to predict the risk of complications and to determine the best management for twin pregnancies. Histopathological examination of the placenta and umbilical cord after delivery can help to confirm prenatal diagnosis and to provide a better understanding of the physiopathology of their abnormalities. The aim of this review was to emphasize the role that the umbilical cord plays in twin complications and to describe the management of these high-risk pregnancies.
Influence of ABCB1, CYP3A5 and CYP3A4 gene polymorphisms on prothrombin time and the residual equilibrium concentration of rivaroxaban in patients with non-valvular atrial fibrillation in real clinical practice
Authors: Sychev Dmitry Alekseevitch , Sokolov Aleksey Vladimirovich , Reshetko Olga Vilorovna , Fisenko Vladimir Petrovich , Sychev Igor Nikolaevich , Grishina Elena Anatolievna , Bochkov Pavel Olegovich , Shevchenko Roman Vladimirovich , Abdullaev Sherzod Pardaboevich , Denisenko Natalia Pavlovna , Ivashchenko Dmitry Vladimirovich , Sozaeva Zhannet Alimovna , Kachanova Anastasia Alekseevna
Published: October 2022

Objective

The study of ABCB1 and CYP3A4/3A5 gene polymorphism genes is promising in terms of their influence on prothrombin time variability, the residual equilibrium concentration of direct oral anticoagulants (DOACs) in patients with atrial fibrillation and the development of new personalized approaches to anticoagulation therapy in these patients. The aim of the study is to evaluate the effect of ABCB1 (rs1045642) C>T; ABCB1 (rs4148738) C>T and CYP3A5 (rs776746) A>G, CYP3A4*22(rs35599367) C>T gene polymorphisms on prothrombin time level and residual equilibrium concentration of rivaroxaban in patients with atrial fibrillation.

Methods

In total 86 patients (42 men and 44 female), aged 67.24 ± 1.01 years with atrial fibrillation were enrolled in the study. HPLC mass spectrometry analysis was used to determine rivaroxaban residual equilibrium concentration. Prothrombin time data were obtained from patient records.

Results

The residual equilibrium concentration of rivaroxaban in patients with ABCB1 rs4148738 CT genotype is significantly higher than in patients with ABCB1 rs4148738 CC (P = 0.039). The analysis of the combination of genotypes did not find a statistically significant role of combinations of alleles of several polymorphic markers in increasing the risk of hemorrhagic complications when taking rivaroxaban.

Conclusion

Patients with ABCB1 rs4148738 CT genotype have a statistically significantly higher residual equilibrium concentration of rivaroxaban in blood than patients with ABCB1 rs4148738 CC genotype, which should be considered when assessing the risk of hemorrhagic complications and risk of drug–drug interactions. Further studies of the effect of rivaroxaban pharmacogenetics on the safety profile and efficacy of therapy are needed.