bluuebunny/crossref_metadata_2025 huggingface dataset:
Child Abuse Imaging and Findings in the Time of COVID-19
Authors: Henry M. Katherine , Wood Joanne N. , Bennett Colleen E. , Chaiyachati Barbara H. , Egbe Teniola I. , Otero Hansel J.
Published: January 2022

Objective

To assess the impact of the COVID-19 pandemic on physical abuse in young children, we compared the following before and during the pandemic: (1) skeletal survey volume, (2) percent of skeletal surveys revealing clinically unsuspected (occult) fractures, and (3) clinical severity of presentation. We hypothesized that during the pandemic, children with minor abusive injuries would be less likely to present for care, but severely injured children would present at a comparable rate to prepandemic times. We expected that during the pandemic, the volume of skeletal surveys would decrease but the percentage revealing occult fractures would increase and that injury severity would increase.

Methods

We conducted a retrospective study of children younger than 2 years undergoing skeletal surveys because of concern for physical abuse at a tertiary children's hospital. Subjects were identified by querying a radiology database during the March 15, 2019–October 15, 2019 (pre–COVID-19) period and the March 15, 2020–October 15, 2020 (COVID-19) period, followed by chart review to refine our population and abstract clinical and imaging data.

Results

Pre–COVID-19, 160 skeletal surveys were performed meeting the inclusion criteria, compared with 125 during COVID-19, representing a 22% decrease. No change was observed in identification of occult fractures (6.9% pre-COVID vs 6.4% COVID, P = 0.87). Clinical severity of presentation did not change, and child protective services involvement/referral decreased during COVID.

Conclusions

Despite a >20% decrease in skeletal survey performance early in the pandemic, the percent of skeletal surveys revealing occult fractures did not increase. Our results suggest that decreases in medical evaluations for abuse did not stem from decreased presentation of less severely injured children.
Emotional Distress, Targeted Rejection, and Antibody Production After Influenza Vaccination in Adolescence
Authors: Corallo Kelsey L. , Lyle Sarah M. , Carlock Michael A. , Ross Ted M. , Ehrlich Katherine B.
Published: January 2022

Objective

The purpose of this study was to explore how both ongoing emotional distress and the experience of a targeted rejection over the past 6 months are associated with adolescents’ antibody response to influenza virus vaccination. We predicted that experiencing a targeted rejection would amplify the hypothesized negative association between emotional distress and antibody response after vaccination.

Methods

Adolescent participants (N = 148) completed two study visits (mean [standard deviation] days between visits = 27.4 [1.8]). At the first visit, they provided blood samples, were administered the seasonal (2018–2019) quadrivalent influenza vaccine (Fluzone, Sanofi Pasteur), completed questionnaires, and participated in a semistructured interview. At the second visit, they provided another blood sample. Hemagglutination-inhibition assays were conducted to determine prevaccination and postvaccination antibody titers. Targeted rejection experiences were coded from adolescents’ interviews.

Results

The emotional distress by targeted rejection interaction predicted antibody response to the two A strains and the composite of all vaccine strains (b values = −0.451 to −0.843, p values < .05), but not the two B strains. Results suggested that, among adolescents who experienced a targeted rejection over the past 6 months, emotional distress was negatively associated with vaccine response (however, this finding did not reach statistical significance). Conversely, among adolescents who did not experience a targeted rejection, emotional distress was positively associated with vaccine response (b = 0.173, p = .032).

Conclusions

The current study highlights the importance of evaluating both acute life events and ongoing distress as they relate to adaptive immune functioning in adolescence.
Respiratory Sinus Arrhythmia as a Physiological Resilience Marker for Children’s Health
Authors: Alen Nicholas V. , Deer LillyBelle K. , Hostinar Camelia E.
Published: January 2022

Objective

The current study aimed to test parasympathetic nervous system activity, indexed through resting respiratory sinus arrhythmia (RSA) as a resilience factor that moderates the associations between socioeconomic status (SES), circulating cytokines, and somatic health in children.

Methods

The sample included 181 parent-child dyads (mean [standard deviation] child age = 9.91 [0.57] years; 50.3% boys). Parents reported on family income, parental education, and subjective social status, to index SES. Children provided serum samples for assaying circulating inflammatory cytokines and had RSA measured during a 5-minute seated resting period. We used a composite measure of inflammation that combined standardized measures of interleukin 6, interleukin 10, and tumor necrosis factor α. Parents reported on their child’s global health impairment and number of chronic health conditions.

Results

Lower SES was associated with poorer global health, and higher levels of inflammation were associated with poorer global health, but these associations were not significant among children with high resting RSA. Specifically, resting RSA moderated the association between SES and global health impairment (B = 0.09, standard error [SE] = 0.02, p < .001). Preliminary evidence suggests that resting RSA may also moderate the association between inflammation and global health impairment (B = −0.12, SE = 0.03, p < .001), although this effect was no longer significant after Winsorizing an outlier value of a child with high global health impairment (B = −0.06, SE = 0.03, p = .04).

Conclusions

High resting RSA may represent a physiological profile of resilience in children, weakening the associations between low SES and poor somatic health, and between greater inflammation and poor somatic health.
Bidirectional Association Between Obsessive-Compulsive Disorder and Systemic Autoimmune Diseases Among Probands and Unaffected Siblings: A Nationwide Population-Based Study
Authors: Liou Ying-Jay , Tsai Shih-Jen , Bai Ya-Mei , Cheng Chih-Ming , Chen Tzeng-Ji , Liang Chih-Sung , Chen Mu-Hong
Published: January 2022

Objective

Studies have reported a biological link between obsessive-compulsive disorder (OCD) and systemic autoimmune disease (SAID). However, whether the unaffected siblings of patients with OCD or SAID are more likely to develop subsequent SAID or OCD later in life remains unclear.

Methods

We examined the Taiwan National Health Insurance Research Database data of 17,135 patients with SAID, 30,672 unaffected siblings, and 467,211 non-SAID reference subjects born before 2000 for subsequent OCD during 1996–2011 and those of 25,364 patients with OCD, 42,546 unaffected siblings, and 654,207 non-OCD reference subjects to identify subsequent SAID during 1996–2011.

Results

Patients with SAID (odds ratio = 1.74, 95% confidence interval = 1.31–2.31) and unaffected siblings (1.25, 0.92–1.70) were more likely to develop OCD later in life than the non-SAID reference group. Moreover, patients with OCD (odds ratio = 1.53, 95% confidence interval = 1.15–2.05) and unaffected siblings (1.51, 1.21–1.87) were more likely to develop any form of SAID during the follow-up than the non-OCD reference group.

Conclusions

The bidirectional association of OCD and SAID between probands and siblings may indicate a familial coaggregation of these two conditions. Additional studies elucidating the genetic and environmental mechanisms underlying this coaggregation are warranted.
Somatic Symptoms in Adolescents With an Ill Parent
Authors: Elliott Lindsey C. , Stager Lindsay M. , Long Dustin , Goodin Burel R. , Fobian Aaron D.
Published: January 2022

Objective

Parent chronic illness may increase somatic symptomology risk in children. The current study examines this association in relation to a variety of chronic illnesses and also considers possible related parental and adolescent background factors.

Methods

Secondary analyses used longitudinal data from the University of North Carolina National Longitudinal Study of Adolescent to Adult Health. Interviews were used to assess demographics, adolescent somatic symptoms, living situation, and parental illness and general physical health. Somatic symptoms in adolescents with no ill parents (n = 2302 adolescents; Mage = 15.3) were compared with adolescents with ill mothers (n = 2336; Mage = 15.3), ill fathers (n = 1304; Mage = 15.3), or two ill parents (n = 3768; Mage = 15.3) using Poisson regression models. We also examined the role of living status, adolescent sex, and parent general physical health on somatic symptom outcomes.

Results

Elevated somatic symptoms were observed in adolescents with ill mothers (mean ratio [MR] = 1.15, p = .015) and with both parents ill (MR = 1.10, p < .001). Among adolescents with ill parents, females had more symptoms than males (ill mother: MR = 1.12, p < .001; ill father: MR = 1.23, p < .001; and both parents ill: MR = 1.23, p < .001). Poorer maternal physical health also increased somatic symptom risk (MR = 1.12, p = .02). Longitudinally, adolescents with ill mothers (MR = 1.14, p < .001), ill fathers (MR = 1.13, p < .001), or both parents ill (MR = 1.16, p < .001) had increased somatic symptom risk. Wave I somatic symptoms also increased future risk: ill mother (MR = 1.19, p < .001), ill father (MR = 1.22, p < .001), or both parents ill (MR = 1.20, p < .001).

Conclusions

The results highlight that having an ill parent is a risk factor for adolescent somatic symptoms. In addition, other factors such as adolescent sex play an additional role in adolescent somatic symptoms.
Impact of low relative skeletal muscle mass and power on the development of metabolic syndrome in Japanese women: a 7-year prospective study
Authors: Yamada Yosuke , Murakami Haruka , Kawakami Ryoko , Gando Yuko , Nanri Hinako , Nakagata Takashi , Watanabe Daiki , Yoshida Tsukasa , Hatamoto Yoichi , Yoshimura Eiichi , Sanada Kiyoshi , Miyatake Nobuyuki , Miyachi Motohiko
Published: January 2022

Previous cross-sectional studies indicated that low relative skeletal muscle mass against body weight (appendicular lean mass divided by body weight, ALM/Wt or divided by body mass index, ALM/BMI) was negatively associated with metabolic syndrome (MetS). The aim of this longitudinal study was to investigate the impact of low relative skeletal muscle mass and leg muscle power on the development of MetS in Japanese women in a 7-y prospective study. Subjects were 346 Japanese women aged 26 to 85 years. The reference values for Class I sarcopenia were defined as values one SD below the sex-specific means of the young group. The longitudinal relation between muscle mass or leg power and development of MetS was examined using Kaplan-Meier curves and Cox regression models (average follow-up duration 7 years, range 1 to 10 years). During follow-up, 24 of subjects developed MetS. Both indices of ALM/Wt or ALM/BMI, the incidence of MetS was higher in Class I sarcopenia group than normal muscle mass group even after controlling variables (adjusted hazard ratio [AHR] = 3.22 [95%CI; 1.25-8.27] for ALM/Wt and 3.19 [95%CI; 1.31-7.74] for ALM/BMI). In contrast, for the leg power per body weight, the incidence of MetS was not significantly different between low leg power and normal leg power groups (AHR = 1.23 [95%CI; 0.50-3.04]). Current longitudinal study indicated that low relative skeletal muscle mass but not low leg power was independent risk factors for the development of MetS in Japanese women.
The computational models of AlphaFold2 and RoseTTAfold carry protein foldability information
Authors: Liu Sen , Wu Kan , Chen Cheng
Published: January 2022

Protein folding has been a “holy grail” problem of biology for fifty years, and the recent breakthrough from AlphaFold2 and RoseTTAfold set a profound milestone for solving this problem. AlphaFold2 and RoseTTAfold were successful in predicting protein structures from peptide sequences with high accuracy. Meanwhile, although the protein folding problem also cares about the kinetic pathways of protein folding, AlphaFold2 and RoseTTAfold were not trained with this functionality. Considering that their training sets contain proteins from foldable sequences and sequence evolutionary information, we wondered if the computational models from AlphaFold2 and RoseTTAfold might carry protein foldability information. To test this idea, we systematically predicted the structural models of 149 circular permutants and 148 alanine insertion mutants of the 149-residue dihydrofolate reductase of Escherichia coli with AlphaFold2 and RoseTTAfold. Our data showed that although AlphaFold2 and RoseTTAfold could not directly identify unfoldable proteins, the structural variations of computational models are correlated with protein foldability. Furthermore, this correlation is independent of secondary structures. Most importantly, the structural variations of computational models are quantitatively correlated with protein foldability but not protein function. Our work could be of great value to the design of circular permutants, the design of fragment complementary proteins, the design of novel proteins, and the development of computational tools for predicting protein folding kinetics.

Highlights

AlphaFold2 and RoseTTAfold could not directly identify unfoldable proteins.

The structural variations of computational models are correlated with protein foldability.

This correlation is independent of secondary structures.

The structural variations of computational models are quantitatively correlated with protein foldability but not protein function.
Prophages divertStaphylococcus aureusdefenses against host lipids
Authors: Zhou Biyang , Pathania Amit , Pant Deepak , Halpern David , Gaudu Philippe , Trieu-Cuot Patrick , Dias-Leao Andressa , Pagot Charlotte , Solgadi Audrey , Gruss Alexandra , Gloux Karine
Published: January 2022

Phages are ubiquitous in bacteria, including clinicalStaphylococcus aureus, where Sfi 21/Sa3 phages often integrate into thehlbgene, encoding Hlb sphingomyelinase. The integration acts as a rapid regulatory switch of Hlb production. Our findings suggest that Sfi 21/Sa3 prophages and Hlb activity affectS. aureusfitness by modulating the incorporation of the toxic linoleic acid (C18:2) from serum into the bacterial membrane. This process relies on C18:2 derived from 1,3-diglyceride, facilitated by the FakB1 kinase subunit. Palmitic acid (C16), primarily released from serum through Hlb activity, competes for FakB1. This mechanism contributes to adaptation to AFN-1252, an antibiotic inhibiting the fatty acid synthesis pathway (anti-FASII). SinceS. aureusrelies on exogenous fatty acids for growth, AFN-1252 treatment leads to increased proportion of membrane C18:2. Moreover, Hlb inhibition, whetherviaprophage insertion, gene inactivation, or enzyme inhibition, delaysS. aureusadaptation, resulting in higher proportionof C18:2 in the membrane. This study sheds light on the role of lipid environments in infections, and may contribute to the accurate prediction of infection risks and therapeutic efficacy. Furthermore, given that both anti-FASII and Hlb inhibitors enhance C18:2 incorporation, they represent potential agents for combined strategies againstS. aureus.
Wastewater monitoring using a novel, cost-effective PCR-based method that rapidly captures the transition patterns of SARS-CoV-2 variant prevalence (from Delta to Omicron) in the absence of conventional surveillance evidence
Authors: Chassalevris Taxiarchis , Chaintoutis Serafeim C. , Koureas Michalis , Petala Maria , Moutou Evangelia , Beta Christina , Kyritsi Maria , Hadjichristodoulou Christos , Kostoglou Margaritis , Karapantsios Thodoris , Papadopoulos Agis , Papaioannou Nikolaos , Dovas Chrysostomos I.
Published: January 2022

Background

The magnitude of Omicron SARS-CoV-2 variant of concern (VOC) global spread necessitates reinforcement of surveillance implementation. Conventional VOC surveillance based on genotyping of clinical samples is characterized by certain challenges related to available sequencing capacity, population sampling methodologies, and demands in terms of time, labor, and resources. Wastewater-based SARS-CoV-2 VOC surveillance constitutes a valuable supplementary practice, since it does not require extensive sampling, and provides information on the prevalence of the disease in a timely and cost-effective manner.

Methods

A highly sensitive real-time RT-PCR assay was developed, for targeted Omicron VOC detection and quantification in wastewater samples. The assay exclusively amplifies sequences with the S:Δ69/70 deletion, thus its performance is not hampered by the presence of the Delta VOC. The method was incorporated in the analysis of composite daily samples taken from the main Wastewater Treatment Plant (WWTP) of Thessaloniki, Greece from 1 December 2021 to 9 January 2022.

Results

The Omicron VOC was detected for the first time in samples from the Thessaloniki WWTP on 19 December 2021. In the following 10-day period, a rapid increase in Omicron sewage viral load was observed with an estimated early doubling time of 1.86 days. The proportion of the total SARS-CoV-2 load attributed to Omicron reached 91.09% on 7 January, revealing a fast Delta-to-Omicron VOC transition pattern. The detection of Omicron in wastewater preceded the outburst of reported (presumable) Omicron cases in the city by approximately 7 days.

Conclusions

The proposed wastewater-based surveillance approach enables rapid, real-time data acquisition on the Omicron VOC prevalence and transmission dynamics. Timely provision of these results to State authorities can readily influence the decision-making process for targeted public health interventions, including control measures, awareness, and preparedness.
Bioelectrical Impedance Analysis in the nutritional assessment and prediction of complications in patients undergoing surgery for head and neck malignancies, A pilot observational study
Authors: Ting Lai Yi , Yee Peh Hui , Abdul Kadir Hanis Binte , Fan Lee Chun , Iyer N. Gopalakrishna , Hway Wong Ting , Ci An Gerald Tay
Published: January 2022

Background

Patients with head and neck malignancies are especially vulnerable to developing malnutrition, which has a significant impact on morbidity and mortality. Identification of high risk patients is hence critical for optimising outcomes.

Objective

It is hypothesised that bioimpedance analysis (BIA) can provide information on nutritional status and risk of perioperative complications in a timely and accurate manner. The study objectives are; to correlate BIA parameters with Subjective Global Assessment (SGA) scores, and determine the association of BIA parameters with common perioperative complications in patients undergoing head and neck surgery.

Method

This is a cohort study of 61 patients who were admitted for elective head and neck surgery from 2018-2019. Prior to surgery, patients were evaluated in a preoperative multidisciplinary allied health professional clinic for formal SGA scoring. Bioelectrical impedance analysis was performed using the Bodystat Quadscan 4000. One-way ANOVA and Fisher ‘s exact test were performed for associations between SGA and BIA parameters and receiver operating characteristic (ROC) curves were plotted for determination of optimal cut-off values of phase angle and Wellness marker in detecting malnutrition and perioperative pneumonia using Youden ‘s Index (YI).

Results

45 males and 16 females with mean ± SD age of 62 ± 1.6 years old were included in the study. Significant differences were observed in Wellness Marker (p=0.004) and phase angle (p=0.006) amongst patients in the 3 SGA categories. BIA parameters (p=0.011 and p=0.032 for Wellness Marker and phase angle respectively) were associated with perioperative pneumonia. No significant differences were observed for other perioperative complications namely surgical site infections, salivary leak/fistula, and flap complications.

Conclusion

Bioelectrical Impedance Analysis is associated with Subjective Global Assessment and shows promise as a preoperative tool, in conjuction with SGA, to detect malnutrition in patients undergoing surgery for head and neck malignancies and highlight patients at risk of developing perioperative pneumonia.
Ready for Impact? A validity and feasibility study of instrumented mouthguards (iMGs)
Authors: Jones Ben , Tooby James , Weaving Dan , Till Kevin , Owen Cameron , Begonia Mark , Stokes Keith , Rowson Steve , Phillips Gemma , Hendricks Sharief , Falvey Éanna , Al-Dawoud Marwan , Tierney Gregory
Published: January 2022

Objectives

Determine the validity and feasibility of current Instrumented mouthguards (iMGs) and associated systems.

Methods

Phase 1; Four iMG systems (Football Research Inc [FRI], HitIQ, ORB, Prevent) were compared against dummy headform laboratory criterion standards (25, 50, 75, 100 g). Phase 2; Four iMG systems were evaluated for on-field validity of iMG-triggered events against video-verification to determine true-positives, false-positives and false-negatives (20 ± 9 player matches per iMG). Phase 3; Four iMG systems were evaluated by eighteen rugby players, for perceptions of fit, comfort and function. Phase 4; Three iMG systems (FRI, HitIQ, Prevent) were evaluated for practical feasibility (system usability scale; SUS) by four practitioners.

Results

Phase 1; Total concordance correlation coefficient was 98.3%, 95.3%, 42.5% and 97.9% for FRI, HitIQ, ORB and Prevent. Phase 2; Different on-field kinematics were observed between iMGs. Positive predictive values were 0.98, 0.90, 0.53 and 0.94 for FRI, HitIQ, ORB and Prevent. Sensitivity values were 0.51, 0.40, 0.71 and 0.75 for FRI, HitIQ, ORB and Prevent. Phase 3; player perceptions of fit, comfort and function were 77%, 6/10, 55% for FRI, 88%, 8/10, 61% for HitIQ, 65%, 5/10, 43% for ORB, and 85%, 8/10, 67% for Prevent. Phase 4; SUS was 51.3-50.6/100, 71.3-78.8/100, and 83.8-80.0/100 for FRI, HitIQ, and Prevent.

Conclusion

This study shows that differences between current iMG systems exist. Sporting organisations can use these findings to ensure accurate head acceleration event data are obtained and system adoption is optimized, to support player welfare initiatives directly related to long-term brain health.
Chronic lithium therapy and urine concentrating ability in individuals with bipolar disorder: association between daily dose and resistance to vasopressin and polyuria
Authors: Tabibzadeh Nahid , Vidal-Petiot Emmanuelle , Cheddani Lynda , Haymann Jean-Philippe , Lefevre Guillaume , Etain Bruno , Bellivier Frank , Marlinge Emeline , Delavest Marine , Vrtovsnik François , Flamant Martin
Published: January 2022

Background and objectives

Chronic lithium treatment in individuals with bipolar disorder can induce nephrogenic diabetes insipidus. However, the prevalence, kinetics and mechanisms of such complication are poorly known. We aimed at evaluating patterns of urine concentrating ability and the correlates of 24-hour urine output in individuals treated with lithium.

Design, setting, participants and measurements

Prospective single center observational study of 217 consecutive individuals treated with lithium carbonate and referred to the renal unit. All individuals collected 24-hour urine the day before admission and underwent a desmopressin (DDAVP) concentrating test, fasting plasma vasopressin measurement (copeptin measurement in a subset of individuals, n=119), and measured GFR (mGFR) using urinary99Tc-DTPA clearance. Maximal urine osmolality (Max Uosm) was defined as the highest level during the DDAVP test.

Results

21% of individuals displayed polyuria (> 3l/day), but 55% displayed elevated fasting vasopressin level (> 5 pg/ml). During the DDAVP test, Uosm was significantly lower, and urinary output and free water clearance were significantly higher in the highest treatment duration tertile (> 10 years) whereas no difference was observed between the first two tertiles (< 2.5 years and 2.5-10 years). Among individuals with normal Max Uosm (>600 mOsm/KgH2O) (n=128), 51% displayed elevated vasopressin levels, which was associated with higher lithium daily doses (950 [750- 1200] versus 800 [500- 1000] mg/d, p<0.001), and 100% of patients with lithium daily dose ≥1400 mg/d had high vasopressin levels. In multivariable analysis, 24-hour urine output was associated with higher lithium daily dose (β 0.49 ± 0.17, p=0.005), female sex (β -359 ± 123, p=0.004), daily osmolar intake (β 2.21 ± 0.24, p<0.001), maximal urine osmolality (β -2.89 ± 0.35, p<0.001) and plasma vasopressin level (β 10.17 ± 4.76, p=0.03), but not with lithium formulation.

Conclusions

Higher lithium daily dose was associated with higher vasopressin levels and higher urine output, independently of other factors. Daily osmolar intake was also associated with higher 24-hour urine output. These results suggest that controlled salt and protein intake and lithium dose might reduce renal resistance to vasopressin in these patients.
Structural basis for kinase inhibition in the tripartiteE. coliHipBST toxin-antitoxin system
Authors: Bærentsen René L. , Nielsen Stine Vang , Skjerning Ragnhild Bager , Lyngsø Jeppe , Bisiak Francesco , Pedersen Jan Skov , Gerdes Kenn , Sørensen Michael A. , Brodersen Ditlev. E.
Published: January 2022

Many bacteria encode multiple toxin-antitoxin (TA) systems targeting separate, but closely related, cellular functions. The toxin of theE. coli hipBAsystem, HipA, is a kinase that inhibits translation via phosphorylation of glutamyl-tRNA synthetase. EnteropathogenicE. coli(EPEC) O127:H6 encodes thehipBA-like, tripartite TA system;hipBST, in which the HipT toxin specifically targets the tryptophanyl-tRNA synthetase, TrpS. Notably, in the tripartite system, the function as antitoxin has been taken over by the third protein, HipS, but the molecular details of how activity of HipT is inhibited remain poorly understood. Here, we show that HipBST is structurally different fromE. coliHipBA and that the unique HipS protein, which is homologous to the N-terminal subdomain of HipA, inhibits the kinase through insertion of a conserved Trp residue into the active site. We also show how auto-phosphorylation at two conserved sites in the kinase toxin serve different roles and affect the ability of HipS to neutralize HipT. Finally, solution structural studies show how phosphorylation affects overall TA complex flexibility.
Brainstem evoked auditory potentials in tinnitus: a best-evidence synthesis and meta-analysis
Authors: Jacxsens Laura , De Pauw Joke , Cardon Emilie , van der Wal Annemarie , Jacquemin Laure , Gilles Annick , Michiels Sarah , Van Rompaey Vincent , Lammers Marc J.W. , De Hertogh Willem
Published: January 2022

Introduction

Accumulating evidence suggests a role of the brainstem in tinnitus generation and modulation. Several studies in chronic tinnitus patients have reported latency and amplitude changes of the different peaks of the auditory brainstem response, possibly reflecting neural changes or altered activity. The aim of the systematic review was to assess if alterations within the brainstem of chronic tinnitus patients are reflected in short- and middle-latency auditory evoked potentials (AEPs).

Methods

A systematic review was performed and reported according to the PRISMA guidelines. Studies evaluating short- and middle-latency AEPs in tinnitus patients and controls were included. Two independent reviewers conducted the study selection, data extraction, and risk of bias assessment. Meta-analysis was performed using a multivariate meta-analytic model.

Results

Twenty-seven cross-sectional studies were included. Multivariate meta-analysis revealed that in tinnitus patients with normal hearing, significantly longer latencies of auditory brainstem response (ABR) waves I (SMD = 0.66 ms, p < 0.001), III (SMD = 0.43 ms p < 0.001), and V (SMD = 0.47 ms, p < 0.01) are present. The results regarding possible changes in middle-latency responses (MLRs) and frequency-following responses (FFRs) were inconclusive.

Discussion

The discovered changes in short-latency AEPs reflect alterations at brainstem level in tinnitus patients. More specifically, the prolonged ABR latencies could possibly be explained by high frequency sensorineural hearing loss, or other modulating factors such as cochlear synaptopathy or somatosensory tinnitus generators. The question whether middle-latency AEP changes, representing subcortical level of the auditory pathway, are present in tinnitus still remains unanswered. Future studies should identify and correctly deal with confounding factors, such as age, gender and the presence of somatosensory tinnitus components.
Left ventricular hypertrophy subtype and long-term mortality in those with subclinical cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Ha Edward T. , Ivanov Alexander , Yeoboah Joseph , Seals Austin , Peterson Stephen J. , Parikh Manish , Aronow Wilbert S. , Frishman William H.
Published: January 2022

The clinical and biochemical profile of differing LVH phenotypes and its effect on long term outcomes is ill-defined. The study investigated the differences in risk profiles and prognostic effect of concentric (CH) and eccentric hypertrophy (EH) on long-term adverse outcomes in a contemporary, ethnically diverse cohort. We analyzed follow-up data over 15 years from the Multi-Ethnic Study of Atherosclerosis study, an ongoing multicenter, prospective population-based study in the United States that enrolled 6,814 participants with subclinical cardiovascular disease between 2000 and 2002. 4,979 participants with left ventricular mass and wall thickness, derived from cardiac MRI at baseline enrollment were included. Descriptive statistics, Kaplan-Meier curves, and regression models were applied. Independent variables associated with CH were Black and Hispanic race/ethnicity, systolic blood pressure, and metabolic syndrome. Independent variables associated with EH were systolic blood pressure, urine creatinine, whereas serum creatinine had an inverse association. The primary endpoint of all-cause death (n=1,137, 22.8%) occurred in 21.7%, 47.4%, and 56.6% of participants with no, concentric, or eccentric hypertrophy, respectively (p<0.001). Age (HR per year = 1.10 [1.09, 1.11], p<0.001), male gender (HR=1.48 [1.29, 1.69], p<0.001), Black race (HR=1.17 [1.005,1.36], p=0.04), fasting glucose (HR=1.005 [1.003, 1.007], p<0.001), baseline creatinine (HR per mg/dL = 1.29 [1.15-1.46], p<0.001), LVEF (HR per 1% = 0.98 [0.98, 0.99], p=0.005), IL-6 (HR per pg/mL = 1.17 [1.12, 1.22], p<0.001), concentric hypertrophy (HR=1.84 [1.41-2.41], p<0.001), and eccentric hypertrophy (HR=2.58 [1.77-3.76], p<0.001) were significant predictors of all-cause mortality. We conclude that CH and EH are two distinct clinical phenotypes of left ventricular hypertrophy with differing gender and racial predisposition, both associated with worse long-term adverse outcomes.
Interaction of surface type, temperature, and week of season on diagnosed concussion risk American football: Bayesian analysis of 8 Seasons of National Football League Data.
Authors: Smoliga James M , Deshpande Sameer K , Binney Zachary O
Published: January 2022

Background: Artificial turf fields and environmental conditions may influence sports concussion risk, but existing research is limited by uncontrolled confounding factors, limited sample size, and the assumption that risk factors are independent of one another. The purpose of this study was to examine how playing surface, time of season, and game temperature relate to diagnosed concussion risk in the National Football League (NFL). Methods: This retrospective cohort study examined data from the 2012-2019 NFL regular season. Bayesian negative binomial regression models were fit to relate how playing surface, game temperature, and week of the season independently related to diagnosed concussion risk and any interactions among these factors. Results: 1096 diagnosed concussions were identified in 1830 games. There was a >99% probability that concussion risk was reduced on grass surface (median Incidence rate ratio (IRR) = 0.78 [95% credible interval: 0.68, 0.89], >99% probability that concussion risk was lower at higher temperatures (IRR=0.85 [0.76,0.95] for each 7.9oC), and >91% probability that concussion risk increased with each week of the season (IRR=1.02 [1.00,1.04]). There was an >84% probability for a surface x temperature interaction (IRR=1.01 [0.96, 1.28]) and >75% probability for a surface x week interaction (IRR=1.02 [0.99, 1.05]). Conclusions: Diagnosed concussion risk is increased on artificial turf compared to natural grass, and this is exacerbated in cold weather and, independently, later in the season. The complex interplay between these factors necessitates accounting for multiple factors and their interactions when investigating sports injury risk factors and devising mitigation methods.
Single-nuclei transcriptomics of dog hippocampus reveals the distinct cellular mechanism of domestication
Authors: Zhou Qi-Jun , Liu Xingyan , Zhang Longlong , Wang Rong , Yin Tingting , Li Xiaolu , Li Guimei , He Yuqi , Ding Zhaoli , Ma Pengcheng , Wang Shi-Zhi , Mao Bingyu , Zhang Shihua , Wang Guo-Dong
Published: January 2022

The process of dog domestication leads to dramatic differences in behavioral traits compared to grey wolves. A class of putative positively selected genes is related to learning and memory, for instance, long-term potentiation and long-term depression. In this study, we constructed a single-nuclei transcriptomic atlas of the dog hippocampus to illustrate its cell types, cell lineage, and molecular features. Using the transcriptomes of 105,057 single-nuclei from the hippocampus of a Beagle dog, we identified 26 cell clusters and a putative trajectory of oligodendrocyte development. Comparative analysis revealed a significant convergence between dog differentially expressed genes (DEGs) and putative positively selected genes (PSGs). 40 putative PSGs were DEGs in the glutamatergic neurons, especially in the cluster 14, which is related to the regulation of nervous system development. In summary, this study provided a blueprint to understand the cellular mechanism of dog domestication.
Purifying selection against spurious splicing signals contributes to the base composition evolution of the polypyrimidine tract
Authors: Yıldırım Buŗcin , Vogl Claus
Published: January 2022

Among eukaryotes, the major spliceosomal pathway is highly conserved. While long introns may contain additional regulatory sequences, the ones in short introns seem to be nearly exclusively related to splicing. Although these regulatory sequences involved in splicing are well-characterized, little is known about their evolution. At the 3’ end of introns, the splice signal nearly universally contains the dimerAG, which consists of purines, and the polypyrimidine tract upstream of this 3’ splice signal is characterized by over-representation of pyrimidines. If the over-representation of pyrimidines in the polypyrimidine tract is also due to avoidance of a premature splicing signal, we hypothesize thatAGshould be the most under-represented dimer. Through the use of DNA-strand asymmetry patterns, we confirm this prediction in fruit flies of the genusDrosophilaand by comparing the asymmetry patterns to a presumably neutrally evolving region, we quantify the selection strength acting on each motif. Moreover, our inference and simulation method revealed that the best explanation for the base composition evolution of the polypyrimidine tract is the joint action of purifying selection against a spurious 3’ splice signal and the selection for pyrimidines . Patterns of asymmetry in other eukaryotes indicate that avoidance of premature splicing similarly affects the nucleotide composition in their polypyrimidine tracts.
ACCURATE DECODING OF THE SPINAL CORD OUTPUT IN HUMANS WITH IMPLANTED HIGH-DENSITY ELECTRODE ARRAYS
Authors: Muceli Silvia , Poppendieck Wigand , Holobar Aleš , Gandevia Simon , Liebetanz David , Farina Dario
Published: January 2022

Invasive electromyography opened a new window to explore motoneuron behaviour in vivo. However, the technique is limited by the small fraction of active motoneurons that can be concurrently detected, precluding a population analysis in natural tasks. Here, we developed a high-density intramuscular electrode for in vivo human recordings along with a fully automatic methodology that could detect the discharges of action potentials of up to 67 concurrently active motoneurons with 99% accuracy. These data revealed that motoneurons of the same pool receive common synaptic input at frequencies up to 75 Hz and that late recruited motoneurons inhibit the discharges of those recruited earlier. These results constitute an important step in the population coding analysis of the human motor system in vivo.
Development of 3D breast cancer models with human T cells expressing engineered MAIT cell receptors
Authors: Dey Madhuri , Kim Myong Hwan , Nagamine Momoka , Karhan Ece , Kozhaya Lina , Dogan Mikail , Unutmaz Derya , Ozbolat Ibrahim T.
Published: January 2022

Immunotherapy has revolutionized cancer treatment with the advent of advanced cell engineering techniques aimed at targeted therapy with reduced systemic toxicity. However, understanding the underlying immune-cancer interactions require development of advanced three-dimensional (3D) models of human tissues. In this study, we developed proof-of-concept 3D tumor models with increasing complexity to study the cytotoxic responses of CD8+ T cells, genetically engineered to express mucosal-associated invariant T (MAIT) cell receptors, towards MDA-MB-231 breast cancer cells. Homotypic MDA-MB-231 and heterotypic MDA-MB-231/human dermal fibroblast (HDF) tumor spheroids were primed with precursor MAIT cell ligand 5-amino-6-D-ribitylaminouracil (5-ARU). Engineered T cells effectively eliminated tumors after a 3-day culture period, demonstrating that the engineered TCR recognized MR1 expressing tumor cells in the presence of 5-ARU. Tumor cell killing efficiency of engineered T cells were also assessed by encapsulating these cells in fibrin, mimicking a tumor extracellular matrix microenvironment. Expression of proinflammatory cytokines such as IFNγ, IL-13, CCL-3 indicated immune cell activation in all tumor models, post immunotherapy. Further, in corroborating the cytotoxic activity, we found that granzymes A and B were also upregulated, in homotypic as well as heterotypic tumors. Finally, a 3D bioprinted tumor model was employed to study the effect of localization of T cells with respect to tumors. T cells bioprinted proximal to the tumor had reduced invasion index and increased cytokine secretion, which indicated a paracrine mode of immune-cancer interaction. Development of 3D tumor-T cell platforms may enable studying the complex immune-cancer interactions and engineering MAIT cells for cell-based cancer immunotherapies.
Neuronal membrane proteasomes homeostatically regulate neural circuit activity in vivo and are required for learning-induced behavioral plasticity
Authors: He Hai-yan , Ramachandran Kapil , McLain Natalie , Faulkner Regina , Ahsan Arifa , Bera Reshmi , Margolis Seth S , Cline Hollis T
Published: January 2022

Protein degradation is critical for brain function through processes that remain poorly understood. Here we investigated the in vivo function of a recently reported neuronal membrane-associated proteasome (NMP) in the brain of Xenopus laevis tadpoles. We demonstrated that NMPs are present in the tadpole brain with biochemistry and electron microscopy, and showed that they actively degrade neuronal activity-induced nascent proteins. Using in vivo calcium imaging in the optic tectum, we showed that acute inhibition of NMP function rapidly increased spontaneous neuronal activity, resulting in hyper-synchronization among tectal neurons. At the circuit level, inhibiting NMPs abolished learning-dependent improvement in a visuomotor behavior paradigm in live animals. Our data provide the first in vivo characterization of NMP functions in the vertebrate nervous system and suggest that NMP-mediated degradation of activity-induced nascent proteins may serve as a homeostatic modulatory mechanism in neurons that is critical for regulating neuronal activity and experience-dependent circuit plasticity.
Evolution of neural activity in circuits bridging sensory and abstract knowledge
Authors: Mastrogiuseppe Francesca , Hiratani Naoki , Latham Peter
Published: January 2022

The ability to associate sensory stimuli with abstract classes is critical for survival. How are these associations implemented in brain circuits? And what governs how neural activity evolves during abstract knowledge acquisition? To investigate these questions, we consider a circuit model that learns to map sensory input to abstract classes via gradient descent synaptic plasticity. We focus on typical neuroscience tasks (simple, and context-dependent, categorization), and study how both synaptic connectivity and neural activity evolve during learning. To make contact with the current generation of experiments, we analyze activity via standard measures such as selectivity, correlations, and tuning symmetry. We find that the model is able to recapitulate experimental observations, including seemingly disparate ones. We determine how, in the model, the behaviour of these measures depends on details of the circuit and the task. These dependencies make experimentally-testable predictions about the circuitry supporting abstract knowledge acquisition in the brain.
Genomic analyses identify key molecules and significant signaling pathways in AZIN1 regulated prostate cancer cells
Authors: Chang Tingxiang , Gu Hanming , Liu James
Published: January 2022

Antizyme inhibitor 1 (AZIN1) is a critical target in prostate cancer, which regulates the adenosine-to-inosine (A to I) RNA editing during the cancer progression. However, the potential signaling pathways and functions remain unknown. Here, our objective is to figure out the functional molecules and signaling pathways by analyzing the RNA-seq data. The GSE189379 was produced by the Illumina HiSeq 2000 (Homo sapiens). The KEGG and GO analyses showed that focal adhesion and proteoglycans are the mainly affected processes in prostate cancer with the loss of AZIN1. Moreover, we identified ten key molecules including FN1, HRAS, CCND1, RAD51, PCNA, TYMS, CASP3, RRM2, BIRC5, and CCNE2. Therefore, this study provides novel knowledge of AZIN1 mediated prostate cancer.
Liver Protein Expression in Nash Mice on a High-Fat Diet
Authors: Varani James , McClintock Shannon D , Knibbs Randall N , Harber Isabelle , Zeidan Dania , Jawad-Makki Mohamed Ali H , Aslam Muhammad N
Published: January 2022

Male MS-NASH mice were maintained on a high-fat diet for 16 weeks with and without red algae-derived minerals. Obeticholic acid (OCA) was used as a comparator in the same strain and diet. C57BL/6 mice maintained on a standard (low-fat) rodent chow diet were used as a control. At the end of the in-life portion of the study, body weight, liver weight, liver enzyme levels and liver histology were assessed. Samples obtained from individual livers were subjected to Tandem Mass Tag labeling / mass spectroscopy for protein profile determination. As compared to mice maintained on the low-fat diet, all high-fat-fed mice had increased whole body and liver weight, increased liver enzyme (aminotransferases) levels and widespread steatosis / ballooning hepatocyte degeneration. Histological evidence for liver inflammation and collagen deposition was also present, but changes were to a lesser extent. A moderate reduction in ballooning degeneration and collagen deposition was observed with mineral supplementation. Control mice on the high-fat diet alone demonstrated multiple protein changes associated with dysregulated fat and carbohydrate metabolism, lipotoxicity and oxidative stress. Cholesterol metabolism and bile acid formation were especially sensitive to diet. In mice receiving multi-mineral supplementation along with the high-fat diet, there was reduced liver toxicity as evidenced by a decrease in levels of several cytochrome P450 enzymes and other oxidantgenerating moieties. Additionally, elevated expression of several keratins was also detected in mineral-supplemented mice. The protein changes observed with mineral supplementation were not seen with OCA. Our previous studies have shown that mice maintained on a high-fat diet for up to 18 months develop end-stage liver injury including hepatocellular carcinoma. Mineral-supplemented mice were substantially protected against tumor formation and other end-state consequences of high-fat feeding. The present study identifies early (16-week) protein changes occurring in the livers of the high-fat diet-fed mice, and how the expression of these proteins is influenced by mineral supplementation. These findings help elucidate early protein changes that contribute to end-stage liver injury and potential mechanisms by which dietary minerals may mitigate such damage.
Photoclick Phase-separating Hydrogels for 3D Cell Culture and Volumetric Bioprinting
Authors: Müller Monica Z. , Bernero Margherita , Qiu Wanwan , Style Robert W. , Müller Ralph , Qin Xiao-Hua
Published: January 2022

Macroporous scaffolds facilitate solute transport and cell-cell communication, but materials allowing forin situpore formation and 3D printing in aqueous solutions are scarce. Here, we introduce an efficient thiol-ene photoclick resin for light-assisted fabrication of cell-compatible macroporous hydrogels via photopolymerization-induced phase separation (PIPS). This resin consists of norbornene-functionalized polyvinyl alcohol, di-thiol crosslinker and dextran sulfate, which can rapidly form a hydrogel with interconnected pores by PIPS. The pore size is tunable in the range of 2-40 μm as a function of light intensity, polymer composition and molecular charge. Unlike conventional methods to porous materials, PIPS uniquely allowsin situpore formation in the presence of living cells, thereby enabling 3D cell culture and bioprinting applications. We demonstrate fast 3D photoencapsulation of living cells, enhanced cell spreading in macroporous hydrogels, and tomographic volumetric bioprinting of cm-scale hydrogel constructs with hierarchical pores within 20 seconds. Collectively, this resin is cell-compatible, low-cost, easy-to-make and highly efficient for PIPS, offering promises for fast photofabrication of living tissues with complex porous structures.
A lymphatic-stem cell interactome regulates intestinal stem cell activity
Authors: Niec Rachel E. , Chu Tinyi , Gur-Cohen Shiri , Schernthanner Marina , Hidalgo Lynette , Pasolli Hilda Amalia , Kataru Raghu P. , Mehrara Babak J. , Pe’er Dana , Fuchs Elaine
Published: January 2022

Barrier epithelia depend on resident stem cells for homeostasis, defense and repair. Intestinal stem cells (ISCs) of the small and large intestines respond to their local microenvironments (niches) to fulfill a continuous demand for tissue turnover, yet the complexity of their niches is still unfolding. Here, we report an extensive lymphatic network that intimately associates with ISCs within these niches. Devising a lymphatic:organoid coculture system, we show that lymphatic-secreted factors maintain ISCs while inhibiting precocious differentiation. Employing a new deconvolution algorithm, BayesPrism, to pair single-cell and spatial transcriptomics, we cartograph the lymphatic ligand:ISC receptor interactomes at high resolution. We unearth crypt lymphatics as a major source of WNT-signaling factors (WNT2, R-SPONDIN-3) known to drive ISC behavior, and REELIN, a hitherto unappreciated ISC regulator secreted by crypt lymphatics. Together, our studies expose lymphatics as a central hub for niche factors that govern the regenerative potential of ISCs.