bluuebunny/crossref_metadata_2025 huggingface dataset:
Disease-associated inosine misincorporation into RNA hinders translation
Authors: Schroader Jacob H , Jones Lindsey A , Meng Ryan , Shorrock Hannah K , Richardson Jared I , Shaughnessy Sharon M , Lin Qishan , Begley Thomas J , Berglund J Andrew , Fuchs Gabriele , Handley Mark T , Reddy Kaalak
Published: August 2022

Failure to prevent accumulation of the non-canonical nucleotide inosine triphosphate (ITP) by inosine triphosphate pyrophosphatase (ITPase) during nucleotide synthesis results in misincorporation of inosine into RNA and can cause severe and fatal developmental anomalies in humans. While the biochemical activity of ITPase is well understood, the pathogenic basis of ITPase deficiency and the molecular and cellular consequences of ITP misincorporation into RNA remain cryptic. Here, we demonstrate that excess ITP in the nucleotide pool during in vitro transcription results in T7 polymerase-mediated inosine misincorporation in luciferase RNA. In vitro translation of inosine-containing luciferase RNA reduces resulting luciferase activity, which is only partly explained by reduced abundance of the luciferase protein produced. Using Oxford Nanopore Direct RNA sequencing, we reveal inosine misincorporation to be stochastic but biased largely towards misincorporation in place of guanosine, with evidence for misincorporation also in place of cytidine, adenosine and uridine. Inosine misincorporation into RNA is also detected in Itpa-null mouse embryonic heart tissue as an increase in relative variants compared with the wild type using Illumina RNA sequencing. By generating CRISPR/Cas9 rat H9c2 Itpa-null cardiomyoblast cells, we validate a translation defect in cells that accumulate inosine within endogenous RNA. Furthermore, we observe hindered cellular translation of transfected luciferase RNA containing misincorporated inosine in both wild-type and Itpa-null cells. We therefore conclude that inosine misincorporation into RNA perturbs translation, thus providing mechanistic insight linking ITPase deficiency, inosine accumulation and pathogenesis.
The superior salinity tolerance of bread wheat cultivar Shanrong No. 3 is unlikely to be caused by elevated Ta-sro1 poly-(ADP-ribose) polymerase activity
Authors: Vogt Sarah , Feijs Karla , Hosch Sebastian , De Masi Raffaella , Lintermann Ruth , Loll Bernhard , Wirthmueller Lennart
Published: August 2022

Structural and biochemical analyses demonstrate that the elevated salinity tolerance of bread wheat cultivar Shanrong No. 3 is unlikely to be caused by elevated Ta-sro1 poly(ADP-ribose) polymerase activity.
Wealth Dynamics in Communities
Authors: Barron Daniel , Guo Yingni , Reich Bryony
Published: August 2022

This article develops a model to explore how favour exchange influences wealth dynamics. We identify a key obstacle to wealth accumulation: wealth crowds out favour exchange. Therefore, households must choose between growing their wealth and accessing favour exchange. We show that low-wealth households rely on favour exchange at the cost of having tightly limited long-term wealth. As a result, initial wealth disparities persist and can even grow worse. We then explore how communities and policymakers can overcome this obstacle. Using simulations, we show that community benefits and place-based policies can stimulate both saving and favour exchange, and in some cases, can even transform favour exchange into a force that accelerates wealth accumulation.
Synovex ONE Grower improves growth performance for at least 200 days in growing beef steers and heifers fed in confinement for slaughter
Authors: Ball Jase J , Taube Patrick C , Hallberg John W , Wood-Follis Stacey L , Dykstra Carleen R , Nadrasik Angela N , Eberhart Nicole L , Jones Shelby L , Borchers Karmella D , Scramlin Jordan A , Bechtol David T , Waite Audie R , Edmonds Matthew D , Herrick Ryan T , Lechtenberg Kelly F , Lawrence Ty E
Published: August 2022

Growth-promoting implants are broadly used in the feedlot industry to improve growth performance and to increase production efficiencies. With cattle being fed longer and to heavier weights, there is demand for extended-release implants that payout for at least 200 d. Our objective was to evaluate feedlot growth of Synovex ONE Grower, a moderate potency (150 mg trenbolone acetate [TBA] and 21 mg estradiol benzoate [EB]), extended-release, growth-promoting implant for 200 d. At four locations (Texas, Idaho, California, and Nebraska), 200 steers (n = 800; d 0 body weight [BW] = 320.2 ± 9.5 kg) and 200 heifers (n = 800; d 0 BW = 311.5 ± 9.5 kg) were blocked by BW and randomized to 1 of 2 treatments: 1) Control, empty subcutaneous needle inserted and extracted from the middle third of one ear; 2) ONE Grower, 150 mg TBA and 21 mg EB extended-release implant administered in middle third of one ear. Treatments were commingled within pen of the same sex (n = 4/site; 2/sex/site) in a split plot design replicated across four sites. Cattle were fed finishing ration ad libitum common to each geographical region at least once daily and were observed for any abnormal health events twice daily. Treatments were administered on d 0. Mid-study implant site evaluations were performed on d 35 or 41. Initial BW was recorded on d 0 and final BW was recorded on d 200 to 204. Cattle were harvested from d 201 to 231; however, carcass data were not collected due to slaughter facility complications brought on by the COVID-19 pandemic. Data were analyzed using the PROC MIXED and PROC GLIMMIX procedures of SAS (Version 9.4, SAS Institute, Cary, NC; P < 0.05), and animal was the experimental unit. There were no treatment × sex interactions (P ≥ 0.052) for any variable. Final BW on d 200 was greater (P < 0.01) for steers and heifers implanted with ONE Grower compared to Control; ONE Grower improved final BW by 5.7% for steers and 3.9% for heifers. Overall average daily gain (ADG) from d 0 to 200 was greater (P < 0.01) for ONE Grower steers and heifers compared to Control with an increase in ADG of 13.1% for steers and 8.9% for heifers. For cattle implanted with ONE Grower, implant retention rates at d 35 or 41 were 95.7% and 96.3% for steers and heifers, respectively. There was no difference (P ≥ 0.32) in percentage deads, removals, or bullers (steers) between treatments. Synovex ONE Grower improved final BW and ADG in feedlot steers and heifers fed for at least 200 d.
Role of cellular senescence in the pathogenesis of systemic sclerosis
Authors: Tsou Pei-Suen , Shi Bo , Varga John
Published: August 2022

Purpose of review

Systemic sclerosis (SSc) is a chronic rheumatic disease that is characterized by immune activation, vasculopathy and fibrosis of the skin and internal organs. It has been proposed that premature onset of ageing pathways and associated senescent changes in cells contribute to the clinical and pathological features of SSc. The aim of this review is to critically review recent insights into the involvement of cellular senescence in SSc.

Recent findings

Cellular senescence plays a critical role in SSc pathogenesis, particularly involving endothelial cells and fibroblasts. Immunosenescence could also contribute to SSc pathogenesis by direct alteration of cellular functions or indirect promotion of defective immune surveillance. Molecular studies have shed some light on how cellular senescence contributes to fibrosis. Recent and planned proof-of-concept trials using senotherapeutics showed promising results in fibrotic diseases, including SSc.

There is increasing evidence implicating cellular senescence in SSc. The mechanisms underlying premature cellular senescence in SSc, and its potential role in pathogenesis, merit further investigation. Emerging drugs targeting senescence-related pathways might be potential therapeutic options for SSc.
Depression Screening and Behavioral Health Integration in Musculoskeletal Trauma Care
Authors: Secrist Eric , Wally Meghan K. , Yu Ziqing , Castro Manuel , Seymour Rachel B. , Hsu Joseph R. ,   on behalf of EMIT Collaborative
Published: August 2022

Objectives:

To report our experiences in implementing a behavioral health integration pathway, including a validated depression screening and referral to care.

Design:

Retrospective case series.

Setting:

Single surgeon's musculoskeletal trauma outpatient practice during calendar year 2019.

Patients:

All patients presenting to the practice during 2019 were included (n = 573).

Intervention:

We piloted the usage of Patient Health Questionnaire (PHQ)-2 and PHQ-9 screening. An evidence-based, real-time treatment protocol embedded in the electronic health record was triggered when a patient screened positive for depression including an automated behavioral health integration pathway.

Main Outcome Measurements:

The percentage of patients screened, the results of the PHQ screening, and the number of patients referred and enrolled in behavioral health programs were collected.

Results:

Of the 573 patients, 476 (83%) received the PHQ-2 screening, 80 (14%) had a current screening on file (within 1 year), and 17 (3.0%) were not screened. One hundred seventy-two patients (36%) had a PHQ-2 score of 2 or greater and completed the PHQ-9; of them, 60 (35% of patients screened with full PHQ-9, 13% of patients screened) screened positive for symptoms of moderate depression (PHQ-9 score ≥10), and 19 (4.0%) reported passive suicidal ideation (PHQ-9 item 9). Fifty of these patients were referred to behavioral health through the pathway, and 8 patients enrolled in the program. Ten patients were not referred because of a technical error that was quickly resolved. Patients reporting suicidal ideation were managed with psychiatric crisis resources including immediate virtual consult in the examination room.

Conclusions:

This case series demonstrates the feasibility of screening patients for depressive symptoms and making necessary referrals to behavioral health in outpatient musculoskeletal trauma care. We identified 50 patients with depression and appropriately triaged them for further care in our community.
Vitamin D deficiency in melanoma patients is associated with worse overall survival: a retrospective cohort study
Authors: Gracia-Darder Inés , Carrera Cristina , Alamon-Reig Francesc , Puig Susana , Malvehy Josep , Podlipnik Sebastian
Published: August 2022

Recent interest has emerged in the protective role of vitamin D in melanoma survival and is the subject of multiple studies with heterogeneous results. Here, we present a retrospective cohort study of 264 patients with invasive melanoma from a tertiary university hospital. The aim of the study was to analyze the relationship between vitamin D levels and prognosis of melanoma patients. We found that lower vitamin D levels are independently associated with worse overall survival in melanoma patients in concordance with previous studies on other populations. Vitamin D deficiency could play a survival role in melanoma patients,. Future prospective studies are needed to investigate the effect of vitamin D supplementation on melanoma outcomes.
Variance from published guidelines and changes in temporal trends in the management of cutaneous malignant melanoma: a 5-year update
Authors: Brownstone Nicholas , Marson Justin W. , Zakria Danny , Farberg Aaron , Rigel Darrell
Published: August 2022

This study aimed to assess the current management of melanoma from relative to present guidelines and determine changes 5 years ago. An eight-question survey was sent to practicing US dermatologists using the same methodology and questions from our JAAD study. Overall, saucerization/scoop biopsy (48%) was the most commonly used method. The most commonly chosen margin for melanoma in-situ (MMIS) removal was 6–10 mm (51% of respondents). For CMM with a depth greater than 1 mm, the most commonly chosen margins were in the 1.1–1.9 cm range (55% of respondents). More respondents referred cases of MMIS and CMM out for treatment as compared to 2016. Academic dermatologists in 2021 were 8% less likely to treat MMIS as compared to all other practice types in 2021, whereas 7% more likely to treat CMM greater than 1 mm. Academic dermatologists in 2016, as compared to 2021, were 4% more likely to treat MMIS and 19% more likely to treat CMM greater than 1 mm. A total of 91% of respondents reported having some change in their management of CMM. Our study findings suggest that a knowledge gap still exists representing a continued educational opportunity to more effectively distribute and implement CMM management guidelines.
Reduction of Catheter-Associated Urinary Tract Infections
Authors: Baker Susan , Shiner Darcy , Stupak Judy , Cohen Vicki , Stoner Alexis
Published: August 2022

Despite the many advancements in infection prevention, catheter-associated urinary tract infections (CAUTI) continue to be problematic for many hospitals. The large urban teaching hospital featured in this article developed a team that consisted of a registered nurse quality Lean coach, bedside nurses from each inpatient nursing unit, physicians, an infection prevention specialist nurse, an education specialist nurse, and members of the quality department to study this matter. The team focused on understanding current practice related to the use and duration of indwelling urinary catheters. It was discovered that while some indwelling urinary catheters were justified, others could have been avoided altogether or removed earlier. Multifaceted measures were instituted at this hospital to decrease indwelling urinary catheter days and reduce CAUTI rates. The team's journey to successfully decreasing indwelling urinary catheter days by 19.79% and CAUTI rates by 38% is highlighted.
Vascularized Fibula TMJ Reconstruction: A Report of Five Cases featuring Computerized Patient-specific Surgical Planning
Authors: Powers David B. , Breeze John , Erdmann Detlev
Published: August 2022

Background:

Mandibular defects involving the condyle represent a complex reconstructive challenge for restoring proper function of the temporomandibular joint because it requires precise bone graft alignment, or alloplastic materials, for complete restoration of joint function. The use of computerized patient-specific surgical planning (CPSSP) technology can aid in the anatomic reconstruction of mandibular condyle defects with a vascularized free fibula flap without the need for additional adjuncts. The purpose of this study was to analyze clinical and functional outcomes after reconstruction of mandibular condyle defects using only a free fibula graft with the assistance of virtual surgery techniques.

Methods:

A retrospective review was performed to identify all patients who underwent mandibular reconstruction utilizing CPSSP with only a free fibula flap without any temporomandibular joint adjuncts after a hemimandibulectomy with total condylectomy.

Results:

From 2018 to 2021, five patients underwent reconstruction of mandibular defects involving the condyle with CPSSP technology and preservation of the native temporomandibular articulating disk. The average age was 62 years (range, 44–73 years). The average follow-up period was 29.2 months (range, 9–46 months). Flap survival was 100% (N = 5). The maximal interincisal opening range for all patients was 22–45 mm with no lateral deviation or subjective joint pain. No patients experienced progressive joint hypomobility or condylar migration.

Conclusion:

The use of CPSSP technology can aid in the anatomic reconstruction of mandibular condyle defects with a vascularized free fibula flap through precise planning and intraoperative manipulation with optimal functional outcomes.
Machine Learning Improves Functional Upper Extremity Use Capture in Distal Radius Fracture Patients
Authors: Sequeira Sean B. , Grainger Megan L. , Mitchell Abigail M. , Anderson Cassidy C. , Geed Shashwati , Lum Peter , Giladi Aviram M.
Published: August 2022

Current outcome measures, including strength/range of motion testing, patient-reported outcomes (PROs), and motor skill testing, may provide inadequate granularity in reflecting functional upper extremity (UE) use after distal radius fracture (DRF) repair. Accelerometry analysis also has shortcomings, namely, an inability to differentiate functional versus nonfunctional movements. The objective of this study was to evaluate the accuracy of machine learning (ML) analyses in capturing UE functional movements based on accelerometry data for patients after DRF repair. In this prospective study, six patients were enrolled 2–6 weeks after DRF open reduction and internal fixation (ORIF). They all performed standardized activities while wearing a wrist accelerometer, and the data were analyzed by an ML algorithm. These activities were also videotaped and evaluated by visual inspection. Our novel ML algorithm was able to predict from accelerometry data whether the limb was performing a movement rated as functional, with accuracy of 90.4% ± 3.6% for within-subject modeling and 79.8% ± 8.9% accuracy for between-subject modeling. The application of ML algorithms to accelerometry data allowed for capture of functional UE activity in patients after DRF open reduction and internal fixation and accurately predicts functional UE use. Such analyses could improve our understanding of recovery and enhance routine postoperative rehabilitation in DRF patients.
Association Between Risk of Obstructive Sleep Apnea and Glaucoma: The Singapore Epidemiology of Eye Diseases Study
Authors: Mehta Anjali , Man Ryan E.K. , Gan Alfred T. , Najjar Raymond P. , Nongpiur Monisha , Lamoureux Ecosse L. , Cheng Ching-Yu , Fenwick Eva K.
Published: August 2022

Précis:

In this population-based, cross-sectional study of Indian and Malay adults in Singapore aged 40 years or above, intermediate or high risk of obstructive sleep apnea (OSA) was associated with 50% higher odds of having glaucoma.

Background/Aims:

The relationship between OSA and glaucoma is unclear. We assessed the association between the risk of OSA and glaucoma in an Asian population.

Materials and Methods:

In this population-based, cross-sectional study, we included Indian and Malay adults aged 40 years or above recruited between 2011 and 2015. Glaucoma was assessed by trained ophthalmologists and classified into primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG). OSA risk was assessed with the Snoring, Tiredness, Observed apnea, High blood pressure, Body mass index, Age, Neck circumference, and male Gender (STOP-Bang) questionnaire and categorized as low risk (<3) or intermediate/higher risk (≥3). We used multivariable logistic regression models to evaluate the relationship between risk of OSA and glaucoma adjusted for key variables, and further stratified for subtype and ethnicity.

Results:

Of the 3126 participants (mean age: 63.1±9.6 y; 52.5% female), 134 (4.3%) had glaucoma, comprising 86 (2.8%) POAG, 22 (0.7%) PACG and 26 (0.8%) secondary glaucomas, and 1182 (37.8%) had an intermediate/higher risk of OSA. Compared with individuals with a low risk of OSA, individuals with intermediate/higher risk had 50% greater odds of having glaucoma (odds ratio: 1.55, 95% confidence interval: 1.03–2.33; P=0.035). We observed a nonsignificant increase in likelihood of having POAG in those with intermediate/higher risk of OSA compared with those with low risk. The OSA-glaucoma relationship was modified by ethnicity, with Malays with intermediate/higher risk of OSA having a 2-fold risk of having any glaucoma (odds ratio: 2.01, 95% confidence interval: 1.12–3.59 P=0.019); while the same elevated risk was not observed for Indians.

Conclusions:

Intermediate or high risk of OSA is associated with 50% higher odds of having glaucoma in our Singaporean population, with a 2-fold higher risk of glaucoma observed in Malays (but not Indians); however a conformational sleep study is needed.
Variables Associated With COVID-19 Vaccination Among Israeli Adolescents and the Need for Targeted Interventions
Authors: Shkalim Zemer Vered , Grossman Zachi , Cohen Herman Avner , Hoshen Moshe , Gerstein Maya , Richenberg Yael , Jacobson Eyal , Grosu Roy , Yosef Noga , Cohen Moriya , Ashkenazi Shai
Published: August 2022

Background:

We aimed to elucidate variables associated with coronavirus disease 2019 (COVID-19) vaccine compliance in adolescents and devise targeted interventions. Our secondary aim was to compare the rates of severe acute respiratory syndrome coronavirus 2 infection, hospitalizations and deaths between vaccinated and unvaccinated adolescents.

Methods:

A retrospective review of electronic medical records was performed on all adolescents 12–17 years of age registered at Clalit Health District in Israel during January 1, 2021, to November 18, 2021, with characterization by vaccination status against COVID-19. Univariate and multivariable analyses were employed to identify predictors of vaccination.

Results:

Of the 43,919 subjects included in the study, 28,207 (64.2%) were vaccinated. Non–ultraorthodox Jewish adolescents had a higher vaccination rate than the minorities Arabs or ultraorthodox Jews (72.5%, 66.2% and 40.5%, respectively, P < 0.001). Adolescents of high socioeconomic status had nearly 2-fold higher vaccination rates than those of low socioeconomic status (80.4% vs 42.3%; P < 0.0001). Adolescents 16–17 years old had a higher rate of COVID-19 vaccination than those 12–15 years old (72.5% vs 60.6%, P < 0.001), as were girls versus boys (64.7% vs 63.8%, P = 0.047). Multivariate analysis identified 3 independent variables that were significantly (P < 0.001) associated with low vaccination: ultraorthodox sector, Arab population, and underlying obesity (hazard rations 0.42, 0.72 and 0.84, respectively). Vaccination was significantly associated with reduced severe acute respiratory syndrome coronavirus 2 infection, hospitalization and death (P < 0.001).

Conclusion:

This study highlights several pediatric populations with low COVID-19 vaccine compliance. Targeted interventions aimed at these populations are suggested with consideration of their special cultural, social and societal characteristics.
Comparison of Clinical Outcomes Between Athletes With Immediate and Delayed Onset of Symptoms Following Sport-Related Concussion
Authors: Trbovich Alicia M. , Kirschler Abigail , Preszler Jonathan , Collins Michael W. , Kontos Anthony P.
Published: August 2022

Objective:

To compare characteristics and clinical outcomes of adolescent athletes with immediate and delayed onset of symptoms following sport-related concussion (SRC). A secondary objective was to describe the symptoms that are delayed and the timing of symptom onset.

Design:

Prospective, repeated measures study.

Setting:

Concussion Specialty Clinic.

Participants:

One hundred fifty-two participants (63.3% men) aged 11 to 24 (15.78 ± 3.47) evaluated within 7 days (3.47 ± 1.66) of sustaining an SRC.

Independent Variable:

Group classification of immediate (IMMEDIATE) or delayed onset of symptoms (DELAYED; >60 seconds following mechanism of injury) through structured clinical interview.

Main Outcome Measures:

Group comparisons on demographic and medical history factors, concussion and clinical profile symptom scores, computerized neurocognitive test scores, vestibular/oculomotor screening scores, and days to medical clearance.

Results:

24.3% of athletes in the sample were DELAYED. The groups did not differ on demographics and medical history. The DELAYED group had increased likelihood of posttraumatic migraine (PTM) as a primary/secondary clinical profile (P = 0.03). Groups did not differ on any other clinical profiles (P > 0.05). Groups did not differ on recovery time (P = 0.47), the IMMEDIATE group higher dizziness on vestibular/ocular motor screening (P = 0.016) and increased likelihood of dizziness being the initial symptom experienced (P < 0 .001).

Conclusions:

The results indicated that delayed onset of symptoms in athletes were relatively common following SRC, supporting continued evaluation of athletes for several days following suspected injuries. Delayed onset of symptoms was associated with PTM, whereas immediate onset was associated with more pronounced vestibular dysfunction, suggesting that clinicians should consider the timing of symptom onset when assessing and treating athletes following SRC.
Association Between Gut Microbiota and Depressive Symptoms: A Cross-Sectional Population-Based Study in South Korea
Authors: Kim Sun-Young , Park Eunkyo , Lim Weon-Jeong , In Kim Soo , Jeon Sang Won , Chang Yoosoo , Ryu Seungho , Kim Hyung-Lae , Kim Han-Na
Published: August 2022

Objective

This study aimed to investigate the association between gut microbiota and depressive symptoms in a large population cohort of Korean adults.

Methods

Overall, 1238 participants were included in the study. Participants were categorized into depressed or non-depressed groups, based on the depressive symptoms reported on the Center for Epidemiologic Studies Rating Scale for Depression, with a cutoff score of 16, and their fecal microbiota was profiled using 16S ribosomal RNA gene sequencing. Several alpha and beta diversity measures were also estimated. The association between depressive symptoms and gut microbiota was analyzed using generalized linear models. The inferred function of the metagenomes was compared between the two groups.

Results

There were no consistent differences in alpha and beta diversity between the depressed and non-depressed groups. However, the continuous measure of depressive symptoms was inversely associated with one of four measures of alpha diversity (Shannon’s diversity, p = .021). We also found a substantial difference between the depressed and non-depressed groups in the Bray-Curtis dissimilarity among the four beta diversity indices (p = .004). Participants whose depressive symptoms exceeded a clinical cutoff score had a lower relative abundance of the genus Faecalibacterium when compared with controls (coefficient = −0.025, q = 0.047). However, the depressed group had a significantly higher abundance of the genus Oscillospira than did the non-depressed group (coefficient = 0.002, q = 0.023).

Conclusions

Our findings contribute to the identification of potential relationships between the gut microbiota and depressive symptoms and provide useful insights for developing microbiota-based interventions for patients with depressive symptoms.
Longitudinal Relationship Between Posttraumatic Stress Symptoms and Physical Symptoms in Military Veterans
Authors: Graham Kristin , Lawrence-Wood Ellie , McFarlane Alexander
Published: August 2022

Objective

This study aimed to assess the temporal relationship of posttraumatic stress disorder (PTSD) symptoms and physical symptoms in a non–treatment-seeking deployed military sample.

Methods

Data were from a longitudinal study of Australian Defence Force personnel deployed to the Middle East Area of Operations between 2010 and 2012 (n = 1871). Predeployment assessment was conducted 4 months before deployment (T1). Of these, 1324 (70.8% retention rate) participated in assessment within 4 months after deployment (T2), and 1122 (60.0%) completed the third time point at 4 years after deployment (T3). PTSD symptoms were assessed with the posttraumatic stress checklist and physical symptoms with a 67-item self-report Health Symptom Checklist. To explore directional influences between symptoms over time, longitudinal cross-lagged association between the modeled latent factors for PTSD symptoms and physical symptoms was estimated using structural equation modeling.

Results

From T1 to T2, there was a significant bidirectional effect with higher physical symptom count at T1 predicting higher PTSD symptom severity at T2 (β = 0.17, p < .001) and higher PTSD symptom severity at T1 predicting higher physical symptom count at T2 (β = 0.13, p < .001). The effect of T2 on T3 was unidirectional. PTSD symptom severity at T2 had no effect on physical symptom count at T3, but physical symptom count at T2 predicted an increase in PTSD symptom severity at T3 (β = 0.11, p = .013).

Conclusions

Considering early physical symptoms and their physiological underpinnings after traumatic exposures could help identify those at risk of later PTSD.
Patterns of objectively measured physical activity differ between men living with and without HIV
Authors: Etzkorn Lacey H. , Liu Fangyu , Urbanek Jacek K. , Heravi Amir S. , Magnani Jared W. , Plankey Michael W. , Margolich Joseph B. , Witt Mallory D. , Palella Frank J. , Haberlen Sabina A. , Wu Katherine C. , Post Wendy S. , Schrack Jennifer A. , Crainiceanu Ciprian M.
Published: August 2022

Objective:

To use accelerometers to quantify differences in physical activity (PA) by HIV serostatus and HIV viral load (VL) in the Multicenter AIDS Cohort Study (MACS).

Methods:

MACS participants living with (PLWH, n = 631) and without (PWOH, n = 578) HIV wore an ambulatory electrocardiogram monitor containing an accelerometer for 1–14 days. PA was summarized as cumulative mean absolute deviation (MAD) during the 10 most active consecutive hours (M10), cumulative MAD during the six least active consecutive hours (L6), and daily time recumbent (DTR). PA summaries were compared by HIV serostatus and by detectability of VL (>20 vs. ≤20 copies/ml) using linear mixed models adjusted for sociodemographics, weight, height, substance use, physical function, and clinical factors.

Results:

In sociodemographic-adjusted models, PLWH with a detectable VL had higher L6 (β = 0.58 mg, P = 0.027) and spent more time recumbent (β = 53 min/day, P = 0.003) than PWOH. PLWH had lower M10 than PWOH (undetectable VL β = −1.62 mg, P = 0.027; detectable VL β = −1.93 mg, P = 0.12). A joint test indicated differences in average PA measurements by HIV serostatus and VL (P = 0.001). However, differences by HIV serostatus in M10 and DTR were attenuated and no longer significant after adjustment for renal function, serum lipids, and depressive symptoms.

Conclusions:

Physical activity measures differed significantly by HIV serostatus and VL. Higher L6 among PLWH with detectable VL may indicate reduced amount or quality of sleep compared to PLWH without detectable VL and PWOH. Lower M10 among PLWH indicates lower amounts of physical activity compared to PWOH.
Giardia and growth impairment in children in high-prevalence settings: consequence or co-incidence?
Authors: Dougherty Michael , Bartelt Luther A.
Published: August 2022

Purpose of review

Giardia is a common intestinal parasite worldwide, and infection can be associated with clear, and sometimes persistent symptomatology. However, in children in high-prevalence settings, it is most often not associated with or is perhaps even protective against acute diarrhea. Nonetheless, recent longitudinal studies in high-prevalence settings increasingly identify an association with long-term outcomes that has been difficult to discern.

Recent findings

Recent studies have made progress in disentangling this apparent paradox. First, prospective, well characterized cohort studies have repeatedly identified associations between Giardia infection, gut function, and child growth. Second, experimental animal and in-vitro models have further characterized the biological plausibility that Giardia could impair intestinal function and subsequently child development through different pathways, depending upon biological and environmental factors. Finally, new work has shed light on the potential for Giardia conspiring with specific other gut microbes, which may explain discrepant findings in the literature, help guide future higher resolution analyses of this pathogen, and inform new opportunities for intervention.

Recent prospective studies have confirmed a high, if not universal, prevalence of persistent Giardia infections in low-and-middle income countries associated with child-growth shortfalls and altered gut permeability. However, the predominance of subclinical infections limits understanding of the true clinical impact of endemic pediatric giardiasis, and global disease burdens remain uncalculated. Integrating the role of Giardia in multipathogen enteropathies and how nutritional, microbial, metabolic, and pathogen-strain variables influence Giardia infection outcomes could sharpen delineations between pathogenic and potentially beneficial attributes of this enigmatic parasite.
Meta-analysis of the amyotrophic lateral sclerosis spectrum uncovers genome instability
Authors: Ziff Oliver J. , Neeves Jacob , Mitchell Jamie , Tyzack Giulia ,   NeuroLINCS consortium,   AnswerALS consortium, Ruiz Carlos Martinez , McGranahan Nicholas , Luisier Raphaelle , Chakrabarti Anob M. , Boulton Simon J. , Kelly Gavin , Humphrey Jack , Patani Rickie
Published: August 2022

Amyotrophic Lateral Sclerosis (ALS) is characterised by progressive motor neuron degeneration but there is marked genetic and clinical heterogeneity1. Identifying common mechanisms of ALS amongst this diversity has been challenging, however, a systematic framework examining motor neurons across the ALS spectrum may reveal unifying insights. Here, we present the most comprehensive compendium of ALS human-induced pluripotent stem cell-derived motor neurons (iPSNs) from 429 donors across 15 datasets including Answer ALS and NeuroLINCS, spanning 10 ALS mutations and sporadic ALS. Using gold-standard reproducible bioinformatic workflows, we identify that ALS iPSNs show common activation of the DNA damage response and p53 signalling, which was replicated in the NYGC ALS postmortem cohort of 203 spinal cord samples. The strongest p53 activation was observed in C9orf72 repeat expansions but was also independently increased in TARDBP, FUS and sporadic subgroups. ALS iPSNs showed extensive splicing alterations and enrichment of SNVs, indels and gene fusions, which may contribute to their damage-induced mutation signature. Our results integrate the global landscape of motor neuron alterations in ALS, revealing that genome instability is a common hallmark of ALS motor neurons and provides a resource to identify future ALS drug targets.
Determinants of the Omega-3 Index in the UK Biobank
Authors: Schuchardt Jan Philipp , Tintle Nathan , Westra Jason , Harris William S.
Published: August 2022

Information on the Omega-3 Index (O3I) in the United Kingdom (UK) are scarce. The UK-Biobank (UKBB) contains data on total plasma omega-3 polyunsaturated fatty acids (n3-PUFA%) and DHA% measured by NMR. The aim of our study was to create an equation to estimate the O3I (eO3I) from these data. We first performed an interlaboratory experiment with 250 random blood samples in which the O3I was measured in erythrocytes by gas chromatography, and total n3% and DHA% were measured in plasma by NMR. The best predictor of eO3I included both DHA% and a derived metric, the total n3%-DHA%. Together these explained 65% of the variability (r=0.832, p<0.0001). We then estimated the O3I in 117,108 UKBB subjects and correlated it with demographic and lifestyle variables in multivariable adjusted models. The mean (SD) eO3I was 5.58% (2.35%) this UKBB cohort. Several predictors were significantly correlated with eO3I (all p<0.0001). In general order of impact and with directionality (- = inverse, + = direct): oily-fish consumption (+), fish oil supplement use (+), female sex (+), older age (+), alcohol use (+), smoking (-), higher waist circumference and BMI (-), lower socioeconomic status and less education (-). Only 20.5% of eO3I variability could be explained by predictors investigated, and oily-fish consumption accounted for 7.0% of that. With the availability of the eO3I in the UKBB cohort we will be in a position to link risk for a variety of diseases with this commonly-used and well-documented marker of n3-PUFA biostatus.
A probabilistic approach for the study of epidemiological dynamics of infectious diseases: basic model and properties
Authors: Giral-Barajas José , Herrera-Nolasco Carlos Ignacio , Herrera-Valdez Marco Arieli , López Sergio I.
Published: August 2022

The dynamics of epidemiological phenomena associated to infectious diseases have long been modelled with different approaches. However, recent pandemic events exposed many areas of opportunity to improve over the existing models. We develop a model based on the idea that transitions between epidemiological stages are alike sampling processes. Such processes may involve more than one subset of the population or they may be mostly dependent on time intervals defined by infectious or clinical criteria. We apply the model to simulate epidemics and obtain realistic case fatality ratios. We also analyse the impact of the proportion of asymptomatic of infected people in the distribution of the total infected population and define a basic reproductive number, which determines the existence of a probabilistic phase transition for the pandemics dynamics. The resulting modelling scheme is robust, easy to implement, and can readily lend itself for extensions aimed at answering questions that emerge from close examination of data trends, such as those emerging from the COVID-19 pandemic, and other infectious diseases.
A Hybrid Machine Learning Model for Estimation of Obesity Levels
Authors: Choudhuri Akash
Published: August 2022

Obesity has always been a problem which has plagued humans for many generations, which, since the 1975, almost doubled to turn into a global epidemic. The current human dependence on technology has contributed to the problem even more, with the effects visibly pronounced in late teenagers and early adults. Researchers till date, have tried numerous ways to determine the factors that cause obesity in early adults.

On that frontier, our hybrid machine-learning model uses the help of some supervised and unsupervised data mining methods like Extremely Randomized Trees, Multilayer Perceptron and XGBoost using Python to detect and predict obesity levels and help healthcare professionals to combat this phenomenon. Our dataset is a publicly available dataset in the UCI Machine Learning Repository, containing the data for the estimation of obesity levels in individuals from the countries of Mexico, Peru, and Colombia, based on their eating habits and physical condition. The proposed model heavily utilizes feature engineering methods and introduces the concept of a hybrid model.

This work has shown improved results over prior works and extensive studies have been undertaken to preserve the robustness of this model.
Serotype specificity and utility of antibodies 5D8/1 and Cox mAB 31A2 for enterovirus diagnostics
Authors: Laiho Jutta E. , Zeissler Marie , Morgan Noel G. , Hyöty Heikki , Richardson Sarah J.
Published: August 2022

A commercially available antibody, Cox mAB 31A2, raised against the VP1 protein of coxsackievirus B3 (CVB3) has been reported as suitable for the detection of CVB3 in diagnostic samples (Ettischer-Schmid 2016). The authors compared this antibody with the widely used, multi-specific, monoclonal anti-VP1 antibody marketed by Dako (clone 5D8/1) and concluded that clone 5D8/1 should not be used to identify enterovirus infections in diagnostic samples. Rather they suggested that Cox mAB 31A2 is preferable for this purpose. Here we address these issues and show that Cox mAB 31A2 can be used successfully to diagnose CVB3 infection in various cell and tissue samples but we demonstrate that it fails to detect many clinically relevant enterovirus types, thereby limiting its use as a general diagnostic reagent for clinical specimens. Rather, we propose that, when used under carefully controlled conditions, clone 5D8/1 should remain the reagent of choice for such purposes.
Assessing the impact of boldine on the gastrocnemius using multiomic profiling at 7 and 28 days post-complete spinal cord injury in young male mice
Authors: Potter Luke A. , Toro Carlos A. , Harlow Lauren , Lavin Kaleen M. , Cardozo Christopher P. , Wende Adam R. , Graham Zachary A.
Published: August 2022

Spinal cord injury (SCI) results in rapid muscle loss. The mechanisms of muscle atrophy have been well-described but there is limited information specific to SCI. Exogenous molecular interventions to slow muscle atrophy in severe-to-complete SCI have been relatively ineffective and the wide-ranging physiologic response to SCI requires the search for novel therapeutic targets. Connexin hemichannels (CxHC) allow non-selective passage of small molecules into and out of the cell. Boldine, a CxHC-inhibiting aporphine found in the boldo tree (Peumus boldus), has shown promising pre-clinical results in slowing atrophy during sepsis and dysferlinopathy. We administered 50 mg/kg/d of boldine to spinal cord transected mice beginning 3 d post-injury. Tissue was collected 7 and 28 d post-SCI and the gastrocnemius was used for multiomic profiling. Boldine did not prevent body or muscle mass loss but attenuated SCI-induced changes in the abundance of proline, phenylalanine, leucine and isoleucine, as well as glucose, 7 d post-SCI. SCI resulted in the differential expression of ~7,700 and ~2,000 genes at 7 and 28 d, respectively, compared to sham animals, with enrichment for pathways associated with ribosome biogenesis, translation and oxidative phosphorylation. Boldine altered the expression of ~150 genes at 7 d and ~110 genes at 28 d post-SCI. Methylation analyses highlighted distinct patterns at both 7 and 28 d following SCI both with and without boldine. Taken together, boldine is not an efficacious therapy to preserve body and muscle mass after complete SCI, though it preserved or attenuated SCI-induced changes across the metabolome, transcriptome and methylome.
The deubiquitylase USP31 controls the Chromosomal Passenger Complex and spindle dynamics
Authors: Bertsoulaki Erithelgi , Glover Hannah L. , Gomes-Neto Joana I. , Pizer Barry , Maiato Helder , Urbé Sylvie , Clague Michael J.
Published: August 2022

We have identified USP31 as a microtubule and centrosome associated deubiquitylase, depletion of which leads to an increase in individual cell mass and defective proliferation. We have examined its dynamics and impact during mitosis. GFP-USP31 associates with the mitotic and central spindles, its levels are increased 2-3-fold in prometaphase compared to asynchronous cells and it is dynamically phosphorylated in a CDK1 dependent manner. We find that USP31 depleted cells display altered spindle morphology and chromosomal segregation errors, whilst stable expression of a catalytically inactive form of USP31 leads to polyploidy. At prometaphase, levels of multiple CPC components are destabilised, most prominently INCENP. Under anaphase conditions, depletion of USP31 impairs the translocation of both endogenous and ectopically expressed INCENP to the spindle mid-zone, whilst expression of catalytically inactive USP31 results in multiple ectopic cleavage furrows. In summary, our data indicate a multifaceted regulatory role for USP31 during mitosis, with a profound impact on chromosomal passenger complex abundance, dynamics and function.
Chitinase-like proteins promoting tumorigenesis through disruption of cell polarity via enlarged endosomal vesicles
Authors: Khalili Dilan , Kunc Martin , Herbrich Sarah , Mueller Anna , Theopold Ulrich
Published: August 2022

Chitinase-like proteins (CLPs) are associated with tissue-remodeling and inflammation but also with several disorders, including fibrosis, atherosclerosis, allergies, and cancer. However, CLP’s role in tumors is far from clear. Here, we utilizeDrosophila melanogasterto investigate the function of CLPs (imaginal disc growth factors; Idgf’s) inRasV12dysplastic salivary glands. We find one of the Idgf’s members,Idgf3, is transcriptionally induced in a JNK-dependent manner via a positive feedback loop mediated by reactive oxygen species (ROS). Moreover, Idgf3 accumulates in enlarged endosomal vesicles (EnVs) that promote tumor progression by disrupting cytoskeletal organization. The process is mediated via the downstream component, αSpectrin, which localizes to the EnVs. Our data provide new insight into CLP function in tumors and identifies specific targets for tumor control.
A tradeoff between acoustic and linguistic feature encoding in spoken language comprehension
Authors: Tezcan Filiz , Weissbart Hugo , Martin Andrea E.
Published: August 2022

When we comprehend language from speech, the phase of the neural response aligns with particular features of the speech input, resulting in a phenomenon referred to as neural tracking. In recent years, a large body of work has demonstrated the tracking of the acoustic envelope and abstract linguistic units at the phoneme and word levels, and beyond. However, the degree to which speech tracking is driven by acoustic edges of the signal, or by internally-generated linguistic units, or by the interplay of both, remains contentious. In this study, we used naturalistic story-listening to investigate (1) whether phoneme-level features are tracked over and above acoustic edges, (2) whether word entropy, which can reflect sentence- and discourse-level constraints, impacted the encoding of acoustic and phoneme-level features, and (3) whether the tracking of acoustic edges was enhanced or suppressed during comprehension of a first language (Dutch) compared to a statistically-familiar but uncomprehended language (French). We first show that encoding models with phoneme-level linguistic features, in addition to acoustic features, uncovered an increased neural tracking response; this signal was further amplified in a comprehended language, putatively reflecting the transformation of acoustic features into internally-generated phoneme-level representations. Phonemes were tracked more strongly in a comprehended language, suggesting that language comprehension functions as a neural filter over acoustic edges of the speech signal as it transforms sensory signals into abstract linguistic units. We then show that word entropy enhances neural tracking of both acoustic and phonemic features when sentence- and discourse-context are less constraining. When language was not comprehended, acoustic features, but not phonemic ones, were more strongly modulated, but in contrast, when a first language is comprehended, phoneme features are more strongly modulated. Taken together, our findings highlight the flexible modulation of acoustic, and phonemic features by sentence and discourse-level constraint in language comprehension, and document the neural transformation from speech perception to language comprehension, consistent with an account of language processing as a neural filter from sensory to abstract representations.
Mammalian N1-adenosine PARylation is a reversible DNA modification
Authors: Musheev Michael U. , Schomacher Lars , Basu Amitava , Han Dandan , Krebs Laura , Scholz Carola , Niehrs Christof
Published: August 2022

Poly-ADP-ribosylation (PARylation) is regarded as a protein-specific modification. However, some PARPs were recently shown to modify DNA termini in vitro. Here we use ultrasensitive mass spectrometry (LC-MS/MS), anti-PAR antibodies, and anti-PAR reagents to show that mammalian DNA is physiologically PARylated and to different levels in primary tissues. Inhibition of PAR glycohydrolase (PARG) increases DNA PARylation, supporting that the modification is reversible. DNA PARylation requires PARP1 and in vitro PARP1 PARylates single-stranded DNA, while PARG reverts the modification. DNA PARylation occurs at the N1-position of adenosine residues to form N1-Poly(ADP-ribosyl)-deoxyadenosine. Through partial hydrolysis of mammalian gDNA we identify PAR-DNA via the diagnostic deamination product N1-ribosyl-deoxyinosine to occur in vivo. We conclude that N1-adenosine PARylation is a novel, reversible DNA modification.