bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Gains in Surgical Outcomes for High-Risk vs Low-Risk Pancreatoduodenectomy with Successive Refinements of Risk-Stratified Care Pathways
Authors: Ayabe Reed I , Prakash Laura R , Bruno Morgan L , Newhook Timothy E , Maxwell Jessica E , Arvide Elsa M , Dewhurst Whitney L , Kim Michael P , Ikoma Naruhiko , Snyder Rebecca A , Lee Jeffrey E , Katz Matthew H G , Tzeng Ching-Wei D
Published: February 2023

Background:

The use of risk-stratified pancreatectomy care pathways (RSPCPs) is associated with reduced length-of-stay (LOS). This study sought to evaluate the impact of successive pathway revisions with the hypothesis that high-risk patients require iterative pathway revisions to optimize outcomes.

Study Design:

A prospectively maintained database (10/2016-12/2021) was evaluated for pancreatoduodenectomy (PD) patients managed with RSPCPs preoperatively assigned based on pancreatic fistula (POPF) risk. Launched in 10/2016 (Version 1-V1), RSPCPs were optimized in 2/2019 (V2) and 11/2020 (V3). Targeted pathway components included earlier nasogastric tube removal, diet advancement, reduced intravenous fluids and opioids, institution-specific drain fluid amylase cutoffs for early day 3 removal, and patient education. Primary outcome was LOS. Secondary outcomes included major complications (Accordion Grade III+), POPF (ISPGS Grade B/C), and delayed gastric emptying (DGE).

Results:

Of 481 patients, 234 were managed by V1 (83 high-risk), 141 V2 (43 high-risk), and 106 V3 (43 high-risk). Median LOS reduction was greatest in high-risk patients with a 7d reduction (pre-RSPCP-12d, V1-9d, V2-7d, V3-5d), compared to low-risk patients (pre-pathway-10d, V1-6d, V2-5d, V3-4d). Complications decreased significantly among high-risk patients (V1-45%, V2-33%, V3-19%, p< 0.001), approaching rates in low-risk patients (V1-21%, V2-20%, V3-14%). POPF (V1-33%, V2-23%, V3-16%, p< 0.001) and DGE (V1-23%, V2-22%, V3-14%, p< 0.001) improved among high-risk patients.

Conclusions:

Risk-stratified pancreatectomy care pathways are associated with reduced LOS, major complications, Grade B/C fistula, and DGE. The easiest gains in surgical outcomes are generated from the immediate improvement in the patients most likely to be fast-tracked, but high-risk patients benefit from successive application of the learning health system model.
Better performance of deep learning pulmonary nodule detection using chest radiography with reference to computed tomography: data quality is matter
Authors: Kim Jae Yong , Ryu Wi-Sun , Kim Dongmin , Kim Eun Young
Published: February 2023

Background

Labeling error may restrict radiography-based deep learning algorithms in screening lung cancer using chest radiography. Physicians also need precise location information for small nodules. We hypothesized that a deep learning approach using chest radiography data with pixel-level labels referencing computed tomography enhances nodule detection and localization compared to a data with only image-level labels.

Methods

National Institute Health dataset, chest radiograph-based labeling dataset, and AI-HUB dataset, computed tomography-based labeling dataset were used. As a deep learning algorithm, we employed Densenet with Squeeze-and-Excitation blocks. We constructed four models to examine whether labeling based on chest computed tomography versus chest X-ray and pixel-level labeling versus image-level labeling improves the performance of deep learning in nodule detection. Using two external datasets, models were evaluated and compared.

Results

Externally validated, the model trained with AI-HUB data (area under curve [AUC] 0.88 and 0.78) outperformed the model trained with NIH (AUC 0.71 and 0.73). In external datasets, the model trained with pixel-level AI-HUB data performed the best (AUC 0.91 and 0.86). In terms of nodule localization, the model trained with AI-HUB data annotated at the pixel level demonstrated dice coefficient greater than 0.60 across all validation datasets, outperforming models trained with image-level annotation data, whose dice coefficient ranged from 0.36-0.58.

Conclusion

Our findings imply that precise labeled data are required for constructing robust and reliable deep learning nodule detection models on chest radiograph. In addition, it is anticipated that the deep learning model trained with pixel-level data will provide nodule location information.
Antibody prevalence after 3 or more COVID-19 vaccine doses in 23,000 immunosuppressed individuals: a cross-sectional study from MELODY
Authors: Pearce Fiona A , Lim Sean H , Bythell Mary , Lanyon Peter , Hogg Rachel , Taylor Adam , Powter Gillian , Cooke Graham S , Ward Helen , Chilcot Joseph , Thomas Helen , Mumford Lisa , McAdoo Stephen P , Pettigrew Gavin J , Lightstone Liz , Willicombe Michelle
Published: February 2023

Objectives

To investigate the prevalence of spike-protein antibodies following at least 3 COVID-19 vaccine doses in immunocompromised individuals.

Design

Cross-sectional study using UK national disease registries of individuals with solid organ transplants (SOT), rare autoimmune rheumatic diseases (RAIRD) and lymphoid malignancies (LM).

Setting

Participants were identified, invited and recruited at home by accessing the NHS Blood and Transplant Registry for those UK individuals who had received a SOT; and the National Disease Registration Service at NHS Digital for identifying individuals within England with RAIRD or LM.

Participants

101972 people were invited, 28411 recruited, and 23036 provided serological data, comprising 9927 SOT recipients, 6516 with RAIRD, and 6593 with LM.

Interventions

Participants received a lateral flow immunoassay for spike-protein antibodies to perform at home together with an online questionnaire.

Main outcome measures

Odds of detectable IgG spike-protein antibodies in immunosuppressed cohorts following at least three COVID-19 vaccine doses by participant demographic, disease type, and treatment related characteristics

Results

IgG spike-protein antibodies were undetectable in 23.3%, 14.1% and 20.7% of the SOT, RAIRD and LM cohorts, respectively. Participants had received three, four or ≥five vaccine doses at the time of testing in 28.5%, 61.8%, and 9.6%, respectively. In all groups, seropositivity was associated with younger age, higher number of vaccine doses and previous COVID-19 infection. Immunosuppressive medication reduced the likelihood of seropositivity: the lowest odds of seropositivity were found in SOT recipients receiving an anti-proliferative agent, calcineurin inhibitor and steroid concurrently, and those treated with anti-CD20 in the RAIRD and LM cohorts.

Conclusions

Approximately one in five individuals with SOT, RAIRD and LM have no detectable IgG spike-protein antibodies despite three or more vaccines, but this proportion reduces with sequential booster doses. Choice of immunosuppressant and disease-type is strongly associated with serological response. Antibody testing could enable rapid identification of individuals who are most likely to benefit from additional COVID-19 interventions.

Trial registration

Clinicaltrials.gov,NCT05148806
Impact of the COVID-19 pandemic on tuberculosis control in Indonesia: a nationwide analysis of programme data and health system vulnerabilities
Authors: Surendra Henry , Elyazar Iqbal RF , Puspaningrum Evelyn , Darmawan Deddy , Pakasi Tiffany T , Lukitosari Endang , Sulistyo Sulistyo , Deviernur Shena M , Fuady Ahmad , Thwaites Guy , van Crevel Reinout , Shankar Anuraj H , Baird J Kevin , Hamers Raph L
Published: February 2023

Background

There are limited measures of the impact of the COVID-19 pandemic on tuberculosis (TB) control in high-burden countries like Indonesia.

Methods

We analysed district-level data of reported TB cases, treatment and deaths, COVID-19 incidence and mortality, health care capacity, economic status, education level, and public health development index from all 514 districts in Indonesia. We compared data before (2016-2019) and during (2020-2021) the pandemic.

Findings

Compared to the preceding year (2019), in the first pandemic year (2020) the TB case notification declined by 31% (from median 172 [IQR 129-244] in 2019 to 119 [IQR 87-170] in 2020 per 100,000 population; 565,669 vs 393,323 cases, respectively); mortality increased by 8% (from median 4·2 [IQR 2·0-7·4] to 5·0 (IQR 3·1-7·5) per 100,000 population; 13,059 vs 14,148 deaths, respectively); and the overall proportion of cases who started treatment declined by 7% (from 98% to 91%). The second pandemic year (2021) saw a partial recovery of case notifications (median 142 [IQR 99-204]; 473,006) and deaths (4·1 [IQR 2·5-6·8]; 12,016), but a persistently reduced treatment coverage (84%). Reductions in TB notifications between districts were associated with higher COVID-19 incidence and fewer per capita GeneXpert machines for TB diagnosis. Likewise, reduced TB treatment coverage was associated with fewer per capita doctors, and increased reported TB deaths was associated with fewer per capita primary health centres, lower per capita domestic expenditure and higher education.

Interpretation

The COVID-19 pandemic significantly, yet unevenly, impacted the national TB control programme across Indonesia, with the greatest impacts in districts with the least resilient health systems.

Funding

Wellcome Africa Asia Programme Vietnam
Clinical Value Of CT-Derived Simulations Of Transcatheter-Aortic-Valve-Replacement In Challenging Anatomies The PRECISE-TAVR Trial
Authors: Hokken Thijmen W , Wienemann Hendrik , Dargan James , van Ginkel Dirk-Jan , Dowling Cameron , Unbehaun Axel , Bosmans Johan , Bader-Wolfe Andreas , Gooley Robert , Swaans Martin , Brecker Stephen J. , Adam Matti , Van Mieghem Nicolas M.
Published: February 2023

Background

Pre-procedural computed tomography planning improves procedural safety and efficacy of transcatheter aortic valve replacement(TAVR). However, contemporary imaging modalities do not account for device-host interactions. This study evaluates the value of pre-procedural computer simulation with FEops HEARTguide™ on overall device success in patients with challenging anatomies undergoing TAVR with a contemporary self-expanding supra-annular transcatheter heart valve.

Methods

This prospective multicenter observational study included patients with a challenging anatomy defined as bicuspid aortic valve, small annulus or severely calcified aortic valve. We compared the heart team’s transcatheter heart valve(THV) planning decision based on 1) conventional multislice computed tomography(MSCT) and 2) MSCT imaging with FEops HEARTguide™ simulations. Clinical outcomes and THV performance were followed up to 30 days.

Results

A total of 77 patients were included(Median age 79.9 years (IQR 74.2-83.8), 42% male). In 35% of the patients, pre-procedural planning changed after FEops HEARTguide™ simulations(change in valve size selection(12%) or target implantation height(23%)). A new permanent pacemaker implantation(PPI) was implanted in 13% and >trace paravalvular leakage (PVL) occurred in 28.5%. The contact pressure index(i.e. simulation output indicating the risk of conduction abnormalities) was significantly higher in patients with a new PPI, compared to those without(16.0%(25th-75thpercentile 12.0-21.0) vs. 3.5%(25th-75th percentile 0−11.3), p<0.01) The predicted PVL was 5.7mL/s(25th-75thpercentile 1.3-11.1) in patients with none-trace PVL, 12.7(25th-75th percentile 5.5-19.1) in mild PVL and 17.7(25th-75thpercentile 3.6-19.4) in moderate PVL(p=0.04).

Conclusion

FEops HEARTguide™ simulations may provide enhanced insights in the risk for PVL or PPI after TAVR with a self-expanding supra-annular THV in complex anatomies.
Genetic mechanisms of 184 neuro-related proteins in human plasma
Authors: Repetto Linda , Chen Jiantao , Yang Zhijian , Zhai Ranran , Timmers Paul R. H. J. , Li Ting , Twait Emma L. , May-Wilson Sebastian , Muckian Marisa D. , Prins Bram P. , Png Grace , Kooperberg Charles , Johansson Åsa , Hillary Robert F. , Wheeler Eleanor , Pan Lu , He Yazhou , Klasson Sofia , Ahmad Shahzad , Peters James E. , Gilly Arthur , Karaleftheri Maria , Tsafantakis Emmanouil , Haessler Jeffrey , Gyllensten Ulf , Harris Sarah E. , Wareham Nicholas J. , Göteson Andreas , Lagging Cecilia , Ikram Mohammad Arfan , van Duijn Cornelia M. , Jern Christina , Landén Mikael , Langenberg Claudia , Deary Ian J. , Marioni Riccardo E. , Enroth Stefan , Reiner Alexander P. , Dedoussis George , Zeggini Eleftheria , Butterworth Adam S. , Mälarstig Anders , Wilson James F. , Navarro Pau , Shen Xia
Published: February 2023

Understanding the genetic basis of neuro-related proteins is essential for dissecting the disease etiology of neuropsychiatric disorders and other complex traits and diseases. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein’s heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-related traits as well as complex diseases such as hypertension, high cholesterol, immune-related disorders, and psychiatric disorders. Integrating with established drug information, we validated 13 combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets for diseases and comorbidities. This consortium effort provides a large-scale proteogenomic resource for biomedical research.
Role of genetics in capturing racial disparities in cardiovascular disease
Authors: Bose Aritra , Platt Daniel E. , Kartoun Uri , Ng Kenney , Parida Laxmi
Published: February 2023

The role of race in medical decision-making has been a contentious issue. Insights from history and population genetics suggest considering race as a differentiating marker for medical practices can be influenced by systemic bias, leading to serious errors. This may negatively impact treatment of complex diseases such as cardiovascular disease (CVD). We seek to identify instrumental variables and independently verifiable epidemiological tests of whether diagnoses and treatments impacting severe cardiovascular conditions are racially linked. Using data from the UK Biobank (UKB), we found minimal, non-significant racial differences in log odds ratio (OR) between a range of cardiovascular outcomes such as atrial fibrillation, coronary artery disease, coronary thrombosis, heart failure and cardiac fatality. Genetics classification with respect to principal components vs. racial identification of Black British showed no significant differences in diagnoses or therapeutics for CVD related diseases and their associated comorbidities. However, Black British had significant risk of association with genetically predisposed risk of CVD as captured by polygenic risk scores (PRS) of CVD (OR=1.12; 95%CI:1.034-1.223;p <0.006) as well as in 14 related traits. We used a sub-population based feature selection method to find Townsend Deprivation Index, smoking history, hypertension, PRS for ischemic stroke, low density lipoprotein cholesterol, and type II diabetes as the top features predicting the ethnographic category of Black British with an AUC of 79.5%. Therefore, PRS can be used to understand racial disparities in disease outcome which is otherwise not reflected in clinical factors such as diagnoses outcome status or therapeutics in large observational cohorts such as UKB. PRS yield better predictive power with underrepresented minorities and can improve clinical decision-making.
Modelling the impact of vaccination and sexual behavior change on reported cases of mpox in Washington D.C
Authors: Clay Patrick A. , Asher Jason M. , Carnes Neal , Copen Casey E. , Delaney Kevin P. , Payne Daniel C. , Pollock Emily D. , Mermin Jonathan , Nakazawa Yoshinori , Still William , Mangla Anil T. , Spicknall Ian H.
Published: February 2023

Background

The 2022 mpox outbreak infected over 30,000 people in the United States. Infections were commonly associated with sexual contact between men. Interventions included vaccination and reductions in sexual partnerships. We estimated the averted infections attributable to each intervention using mathematical modeling.

Methods

We fit a dynamic network transmission model to mpox cases reported by the District of Columbia through January 2023. We incorporated vaccine administration data and reported reductions in sexual partnerships among gay, bisexual, or other men who have sex with men (MSM). Model output consisted of predicted cases over time with or without vaccination and/or behavior change.

Results

We estimated initial case reductions were due to behavior change. Vaccination alone averted 64% [IQR:57%-72%] and behavior change alone averted 21% [IQR:11%-29%] of cases. Vaccination and behavior change together averted 80% [IQR:74%-85%] of cases. In the absence of vaccination, behavior change reduced cumulative cases but also prolonged the outbreak.

Conclusions

Initial case declines were likely caused by behavior change, but vaccination averted more cases overall. Overall, this indicates that encouraging individuals to protect themselves was vital in the early outbreak, but that combination with a robust vaccination program was ultimately required for control.
Iron metabolism disorders of patients with chronic paracoccidioidomycosis
Authors: de Brito Eliana da Costa Alvarenga , Siqueira Igor Valadares , Venturini James , Félix Vinícius Lopes Teodoro , dos Santos Alana Oswaldina Gavioli Meira , Mendes Rinaldo Poncio , Weber Simone Schneider , Paniago Anamaria Mello Miranda
Published: February 2023

Paracoccidioidomycosis (PCM) is caused byParacoccidioidesspp.; during infection, some host mechanisms limit the availability of iron, thereby reducing its reproduction. However,Paracoccidioidesspp. can evade the immune defense and, even under limited iron conditions, use this mineral for growth and dissemination. This study evaluated the iron metabolism of 39 patients who were diagnosed with chronic PCM between 2013 and 2021. The forms of iron before treatment and at the time of clinical cure were evaluated based on the following: serum ferritin levels (storage iron); total iron-binding capacity (TIBC) and transferrin saturation (TSAT) level (transport iron); red blood cell (RBC), hemoglobin (Hb), hematocrit (HCT), and soluble transferrin receptor (sTfR) levels; and sTfR/log ferritin ratio (functional iron). The mean age of the patients was 54.5 years (±6.7 years). Most patients were men (97.4%), rural workers (92.1%), and smokers (84.6%); most had moderate disease severity (66.7%). Before treatment, the median values of all evaluated parameters were within or just slightly outside the normal range of values. However, it is possible to infer that PCM interferes with functional and storage iron because improvements in these parameters after treatment as well as associations with disease severity were observed. Furthermore, moderate correlations were observed between C-reactive protein and the Hb (r=-0.500; p=0.002), RBC (r=-0.461; p=0.005), HCT (r=-0.514; p=0.001), and iron levels (r=-0.491; p=0.002). PCM interferes with iron metabolism by transforming functional iron to storage iron, as revealed by anemia, low iron levels with normal TSAT levels, normal TIBC, normal sTfR levels, normal sTfR/log ferritin ratios, and normal or slightly increased ferritin levels. PCM can lead to anemia of inflammation, which can be differentiated from iron deficiency anemia by a careful investigation of the iron form parameters.
Prevalence of Carpal Tunnel Syndrome and its associated factors among patients with musculoskeletal compliant at Dilchora Referral Hospitals in Dire Dawa administration, Eastern Ethiopia, 2022
Authors: Yesuf Tewodros , Aragie Hailu , Asmare Yared
Published: February 2023

Background

Carpal tunnel syndrome (CTS) is a chronic focal mono-neuropathy caused by mechanical distortion of the nerve at the carpal tunnel. It is thought to affect between 4 and 5 % of people worldwide, 50 per1000 persons in developed countries, 12.1% in east Africa and 29.2% Ethiopia. The common risk factors include but not limited to, age, sex, inflammatory conditions, pregnancy, diabetes mellitus, and hypertension. Despite this, carpal tunnel syndrome prevalence and its associated factors among patients with musculoskeletal complaints are unaddressed.

Objectives

This study’s aim was to assess the prevalence of carpal tunnel syndrome and its associated factors among patients with musculoskeletal complaints in Dire Dawa, Eastern Ethiopia.

Methodology

An institution-based cross-sectional study was conducted from June 1 to 30, 2022 at Dilchora referral hospital. 265 study participants were selected using the systematic sampling technique. Interviewing techniques and physical examination of the hands and wrists were used to get the data. Epi Data version 3.1 was used to enter, clean up, and edit the data before exporting it for analysis to SPSS version 23.0 software. Bivariable and multivariable logistic regression were carried out with a 95% confidence interval to identify the association of independent and dependent variables. A P-value of 0.05 was considered statistically significant.

Result

A total of 260 respondents were included in this study. The prevalence of clinically proven carpal tunnel syndrome among study participants was 10.8%, with a 95 % CI of (6.99 to 14.6). A multivariable analysis found that being female (AOR: 3.26 (95% CI: 1.05, 10.08), being physically inactive (AOR: 6.32 (95% CI: 1.95, 20.52), diabetes mellitus (AOR: 4.23 (95% CI: 1.47, 11.97)), hypertension (AOR: 6.07 (95% CI: 1.70, 21.65)), hand ratio ≤2.1 (AOR: 7.31(95% CI: 1.80, 29.66)), and wrist ratio ≥ 0.72 (AOR: 5.94 (95% CI: 2.11, 16.72)) were statistically associated factors of carpal tunnel syndrome. But, BMI were not statistically associated with CTS.

Conclusion

The prevalence of carpal tunnel syndrome among patients with musculoskeletal compliant was 10.8%. Several risk factors for CTS have been identified.
Phenome-wide Investigation of Behavioral, Environmental, and Neural Associations with Cross-Disorder Genetic Liability in Youth of European Ancestry
Authors: Paul Sarah E. , Colbert Sarah M.C. , Gorelik Aaron J. , Hansen Isabella S. , Nagella I. , Blaydon L. , Hornstein A. , Johnson Emma C. , Hatoum Alexander S. , Baranger David A.A. , Elsayed Nourhan M. , Barch Deanna M. , Bogdan Ryan , Karcher Nicole R.
Published: February 2023

Etiologic insights into psychopathology may be gained by using hypothesis-free methods to identify associations between genetic risk for broad psychopathology and phenotypes measured during adolescence, including both markers of child psychopathology and intermediate phenotypes such as neural structure that may link genetic risk with outcomes. We conducted a phenome-wide association study (phenotype n=1,269-1,694) of polygenic risk scores (PRS) for broad spectrum psychopathology (i.e., Compulsive, Psychotic, Neurodevelopmental, and Internalizing) in youth of PCA-selected European ancestry (n=5,556; ages 9-13) who completed the baseline and/or two-year follow-up of the ongoing Adolescent Brain Cognitive DevelopmentSM (ABCD) Study. We found that Neurodevelopmental and Internalizing PRS were significantly associated with a host of proximal as well as distal phenotypes (Neurodevelopmental: 187 and 211; Internalizing: 122 and 173 phenotypes at baseline and two-year follow-up, respectively), whereas Compulsive and Psychotic PRS showed zero and one significant associations, respectively, after Bonferroni correction. Neurodevelopmental PRS were further associated with brain structure metrics (e.g., total volume, mean right hemisphere cortical thickness), with only cortical volume indirectly linking Neurodevelopmental PRS to grades in school. Genetic variation influencing risk to psychopathology manifests broadly as behaviors, psychopathology symptoms, and related risk factors in middle childhood and early adolescence.
Clinical genome sequencing: three years’ experience at a tertiary children’s hospital
Authors: Kumar Runjun D. , Saba Lisa F. , Streff Haley , Lopez-Terrada Dolores , Scull Jennifer
Published: February 2023

Introduction

Genome sequencing (GS) may shorten the diagnostic odyssey for patients, but clinical experience with this assay in non-research settings remains limited. Texas Children’s Hospital began offering GS as a clinical test to admitted patients in 2020, providing an opportunity to study how GS is utilized, potential for misorders, and outcomes of testing.

Methods

We conducted a retrospective review of GS orders for admitted patients for a nearly 3-year period from March 2020 through December 2022. We gathered anonymized clinical data from the electronic health record to answer the study questions.

Results

The diagnostic yield over 97 admitted patients was 35%. The majority of GS clinical indications were neurologic or metabolic (61%) and most patients were in intensive care (58%). Tests were often characterized as misordered (56%), frequently due to redundancy with prior testing. Patients receiving GS without prior exome sequencing (ES) had higher diagnostic rates (45%) than the cohort as a whole. In two cases, GS revealed a molecular diagnosis that is unlikely to be detected by ES.

Conclusions

The performance of GS in clinical settings likely justifies its use as a first-line diagnostic test, but the incremental benefit for patients with prior ES may be limited.
Sleep-Disordered Breathing Destabilizes Ventricular Repolarization
Authors: Solhjoo Soroosh , Haigney Mark C. , Siddharthan Trishul , Koch Abigail , Punjabi Naresh M.
Published: February 2023

Rationale

Sleep-disordered breathing (SDB) increases the risk of cardiac arrhythmias and sudden cardiac death.

Objectives

To characterize the associations between SDB, intermittent hypoxemia, and the beat-to-beat QT variability index (QTVI), a measure of ventricular repolarization lability associated with a higher risk for cardiac arrhythmias, sudden cardiac death, and mortality.

Methods

Three distinct cohorts were used for the current study. The first cohort, used for cross-sectional analysis, was a matched sample of 122 participants with and without severe SDB. The second cohort, used for longitudinal analysis, consisted of a matched sample of 52 participants with and without incident SDB. The cross-sectional and longitudinal cohorts were selected from the Sleep Heart Health Study participants. The third cohort comprised 19 healthy adults exposed to acute intermittent hypoxia and ambient air on two separate days. Electrocardiographic measures were calculated from one-lead electrocardiograms.

Results

Compared to those without SDB, participants with severe SDB had greater QTVI (-1.19 in participants with severe SDB vs. -1.43 in participants without SDB,P= 0.027), heart rate (68.34 vs. 64.92 beats/minute;P= 0.028), and hypoxemia burden during sleep as assessed by the total sleep time with oxygen saturation less than 90% (TST90; 11.39% vs. 1.32%,P< 0.001). TST90, but not the frequency of arousals, was a predictor of QTVI. QTVI during sleep was predictive of all-cause mortality. With incident SDB, mean QTVI increased from -1.23 to -0.86 over 5 years (P= 0.017). Finally, exposing healthy adults to acute intermittent hypoxia for four hours progressively increased QTVI (from -1.85 at baseline to -1.64 after four hours of intermittent hypoxia;P= 0.016).

Conclusions

Prevalent and incident SDB are associated with ventricular repolarization instability, which predisposes to ventricular arrhythmias and sudden cardiac death. Intermittent hypoxemia destabilizes ventricular repolarization and may contribute to increased mortality in SDB.
Catchii: empowering literature review screening in healthcare
Authors: Halman Andreas , Oshlack Alicia
Published: February 2023

A systematic review is a type of literature review that aims to collect and analyse all available evidence from the literature on a particular topic. The process of screening and identifying eligible articles from the vast amounts of literature is a time-consuming task. Specialized software has been developed to aid in the screening process and save significant time and labour. However, the most suitable software tools that are available often come with a cost or only offer either a limited or a trial version for free.

In this paper, we report the release of a new software application, Catchii, which contains all the necessary features of a systematic review screener application while being completely free. It supports a user at different stages of screening, from detecting duplicates to creating the final flowchart for a publication. Catchii is designed to provide a good user experience and streamline the screening process through its clean and user-friendly interface on both computers and mobile devices, as well as features such as multi-coloured keyword highlighting, the ability to screen titles and abstracts smoothly with an unstable or even absent internet connection, and more.

Catchii is a valuable addition to the current selection of systematic review screening applications that also allows researchers without financial capabilities to access many of the features found in the best paid tools. Catchii is available athttps://catchii.org
Concurrent Transcranial Magnetic Stimulation and Electroencephalography Measures are Associated with Antidepressant Response from rTMS Treatment for Depression
Authors: Bailey Neil W. , Hoy Kate E. , Sullivan Caley M. , Allman Brienna , Rogasch Nigel C. , Daskalakis Zafiris J. , Fitzgerald Paul B
Published: February 2023

Background

Response rates to repetitive transcranial magnetic stimulation (rTMS) for depression are 25-45%. Biomarkers predicting response to rTMS may reduce treatment burden. TMS-evoked neural activity recorded via electroencephalography (EEG) has potential as a biomarker of treatment response. We examined whether these measures could differentiate responders and non-responders to rTMS for depression.

Methods

Thirty-nine patients with treatment-resistant major depressive disorder (MDD) and 21 healthy controls received TMS during EEG recordings (TMS-EEG). MDD participants then completed 5-8 weeks of rTMS treatment. Repeated measures ANOVAs compared N100 amplitude, N100 slope, and theta power across 3 groups (responders, non-responders and controls), 2 hemispheres (left, F3, and right, F4), and 2 stimulation types (single pulse and paired pulses with a 100ms inter-pulse interval [pp100]).

Results

Neither N100 amplitude nor theta power differed between responders and non-responders. The control group showed more negative N100 amplitudes than the combined depression group. Responders showed a steeper negative N100 slope for single pulses and steeper positive slope for pp100 pulses at F3 than non-responders. Exploratory analyses suggested this may have been due to the responder group showing larger late P60 and N100 amplitudes. Receiver Operator Characteristic (ROC) curve analysis indicated the difference between single and pp100 slopes provided excellent sensitivity (1.00), but poor specificity (0.455).

Limitations

Our study had a small sample size.

Conclusion

Left hemisphere TEPs, in particular N100 slope, may be useful in predicting non-responders to rTMS treatment for depression. Non-response prediction may be useful in saving clinical resources and patient time.
Moderating the link between discrimination and adverse mental health outcomes: Examining the protective effects of cognitive flexibility and emotion regulation
Authors: Zhu Yutong , Deng Wisteria
Published: February 2023

Discrimination is associated with mental health problems. While prior research has demonstrated the significance of emotion regulation in explaining the onset and development of discrimination-related anxiety, few studies investigated this dynamic with cognitive flexibility among sexual and/or racial minority individuals. The current study incorporated cognitive flexibility to investigate its potential buffering effects on discrimination-related anxiety. 221 individuals, 37.6% of whom (n= 83) identified as sexual and/or racial minorities, responded to an online questionnaire about their levels of cognitive flexibility and emotion regulation, perceived discrimination, and anxiety. Moderated mediation analyses were conducted with these variables. Our findings indicated that emotion regulation difficulty (ERD) mediated the relationship between discrimination and anxiety, while cognitive flexibility had a strong moderating effect on the relationship between ERD and anxiety. These results suggested new research directions and implied the therapeutic potential of advancing cognitive flexibility skills with emotion regulation training in anxiety prevention and treatments. Future research is needed to investigate cognitive flexibility as a transdiagnostic mechanism underlying the onset and development of anxiety, to potentially lead to novel prevention or intervention for marginalized people facing additional stressors like discrimination.
Bicycle Helmet Influence in the New Millennium on United States Head, Traumatic Brain Injury, Upper and Lower Body Injury Rates
Authors: Gillham Chris
Published: February 2023

This study compares cycling participation and helmet wearing survey results with bicycle-related total injuries, head injuries, traumatic brain injuries and upper/lower body injuries for all-ages, youth and adults who presented to emergency departments or were hospitalized in the United States from 2001 to 2020. Demographic increases/decreases in bicycle-related total injuries concur with participation survey trends, and this is reflected through injury trends for body parts not influenced by helmet wearing. The decrease in 0-17yo total ED presentations from 2001-2010 to 2011-2020 was greater than the decrease in head injuries but the decrease in total hospital admissions was less than the decrease in hospitalized head injuries. The TBI proportion of 0-17yo head injury ED presentations increased significantly, and to a lesser extent among hospitalized head injuries. 18yo+ head injury ED presentations increased at a significantly greater rate than total injuries from 2001-2010 to 2011-2020. 18yo+ hospital admissions more than doubled and head injuries increased 81.6%. The TBI proportion among 18yo+ ED head injuries increased by 9%, while the hospitalized head injury TBI proportion increased from 84.2% to 86.8%. Future studies should examine the relationship between cycling participation and head injuries to determine why total youth injuries including head injury declines were commensurate with participation declines, why adult total injuries including head injuries increased at rates above estimated participation trends, and why the TBI proportion of head injuries has increased despite a greater number of cyclists wearing helmets since 2001.
A new genetic method for diet determination from faeces that provides species level resolution in the koala
Authors: Blyton Michaela D. J. , Brice Kylie L. , Heller-Uszynska Katarzyna , Pascoe Jack , Jaccoud Damian , Leigh Kellie A. , Moore Ben D.
Published: February 2023

An animal’s diet is a crucial trait that defines their realised ecological niche, especially for dietary specialists such as the koala (Phascolarctos cinereus), a threatened arboreal marsupial folivore. Unfortunately, the current methods used to characterise koala diet are labour intensive, biased and/or unreliable. Further, in this study we show that four barcoding genes (ITS, ETS, CCRandmatK) are unable to resolve potential koala food trees to species. Therefore, we developed and tested a novel SNP-based method for the analysis of koala diet from faeces using the DArTseq platform. This method returned a large number of species-specific SNPs for candidate koala food tree species. Due to low within-species variation, few individuals of each tree species are needed to capture the majority of DArTseq SNP diversity. Nonetheless, we suggest sampling multiple trees to reduce the impact of high allele dropout rates in the DArTseq data. After identifying species-specific SNPs from candidate food tree species from two study sites with different assemblages of eucalypts we were able to detect those SNPs in koala faecal DNA using DArTag, a targeted genotyping assay. This enabled us to semi-quantitatively characterise the koalas’ diets. The food tree species identified were in broad agreement with previously known koala food tree species but also revealed additional species that may contribute to koala diet. This approach provides an important new tool for use in koala ecology and conservation and may prove useful in diet determination for other species where high taxonomic resolution is crucial and dietary DNA is scarce.
A bench-top dark-root device built with LEGO® bricks enables a non-invasive plant root development analysis in soil conditions mirroring nature
Authors: Dermendjiev Georgi , Schnurer Madeleine , Stewart Ethan , Nägele Thomas , Marino Giada , Leister Dario , Thür Alexandra , Plott Stefan , Jeż Jakub , Ibl Verena
Published: February 2023

Roots are the hidden parts of plants, anchoring their above ground counterparts in the soil. They are responsible for water and nutrient uptake, as well as for interacting with biotic and abiotic factors in the soil. The root system architecture (RSA) and its plasticity are crucial for resource acquisition and consequently correlate with plant performance, while being highly dependent on the surrounding environment, such as soil properties and therefore environmental conditions.

Thus, especially for crop plants and regarding agricultural challenges, it is essential to perform molecular and phenotypic analyses of the root system under conditions as near as possible to nature (#asnearaspossibletonature). To prevent root illumination during experimental procedures, which would heavily affect root development, dark-root (D-Root) devices (DRDs) have been developed. In this article, we describe the construction and different applications of a sustainable, affordable, flexible, and easy to assemble open-hardware bench-top LEGO® DRD, the DRD-BIBLOX (Brick Black Box).

The DRD-BIBLOX consists of one or more 3D-printed rhizoboxes which can be filled with soil, while still providing root visibility. The rhizoboxes sit in a scaffold of secondhand LEGO® bricks, which allows root development in the dark as well as non-invasive root-tracking with an infrared (IR) camera and an IR light emitting diode (LED) cluster.

Proteomic analyses confirmed significant effects of root illumination on barley root and shoot proteome. Additionally, we confirmed the significant effect of root illumination on barley root and shoot phenotypes. Our data therefore reinforces the importance of the application of field conditions in the lab and the value of our novel device, the DRD-BIBLOX.

We further provide a DRD-BIBLOX application spectrum, spanning from investigating a variety of plant species and soil conditions as well as simulating different environmental conditions and stresses, to proteomic and phenotypic analyses, including early root tracking in the dark.
Light sensitive short hypocotyl (LSH) confer symbiotic nodule identity in the legume Medicago truncatula
Authors: Schiessl K. , Lee T. , Orvosova M. , Bueno-Batista M. , Stuer N. , Bailey P.C. , Mysore K.S. , Wen J. , Oldroyd G.E.D
Published: February 2023

Legumes grow specialized root nodules that are distinct from lateral roots in morphology and function, with nodules intracellularly hosting beneficial nitrogen-fixing bacteria that provide the plant with a nitrogen source. We have previously shown that a lateral root-like program underpins nodule initiation, but there must be additional developmental programs that confer nodule identity. Here, we show that two members of theLIGHT SENSITIVE SHORT HYPOCOTYL (LSH)transcription factor family, predominantly known to define organ boundaries and meristem complexity in the shoot, function as regulators of nodule organ identity.LSH1/LSH2function upstream of and together with the known nodule regulatorsNuclear Factor Y-A1andNODULE ROOT1/2.The principal outcome ofLSH1/LSH2function is the production of cells able to accommodate nitrogen-fixing bacteria, the unique nodule feature. We conclude that the coordinate recruitment of a pre-existing primordium identity program, in parallel to a root initiation program, underpins the divergence between lateral roots and nodules.
Development and Validation of an MRI-Derived Head-Neck Finite Element Model
Authors: Bahreinizad Hossein , Chowdhury Suman K. , Paulon Gustavo , Wei Leonardo , Santos Felipe Z.
Published: February 2023

Purpose

This study aimed to develop and validate a magnetic resonance imaging (MRI)-based biofidelic head-neck finite element (FE) model comprised of scalp, skull, CSF, brain, dura mater, pia mater, cervical vertebrae, and discs, 14 ligaments, and 42 neck muscles.

Methods

We developed this model using head and neck MRI images of a healthy male participant and by implementing a novel meshing algorithm to create finer hexahedral mesh structures of the brain. The model was validated by replicating four experimental studies: NBDL’s high acceleration profile, Ito’s frontal impact cervical vertebrae study, Alshareef’s brain sonomicrometry study, and Nahum’s impact study.

Results

The results showed reasonable geometrical fidelity. Our simulated brain displacement and cervical disc strain results were close to their experimental counterparts. The intracranial pressure and brain stress data of our head-only model (excluding neck structures and constraining the base of the skull) were similar to Nahum’s reported results. As neck structures were not considered in Nahum’s study, the FE results of our head-neck model showed slight discrepancies. Notably, the addition of neck structures (head-neck model) reduced brain stress values and uncovered the brain’s intracranial pressure dynamics, which the head-only model failed to capture. Nevertheless, the FE simulation results showed a good agreement (r > 0.97) between the kinematic responses of the head-neck model and NBDL’s experimental results.

Conclusion

The developed head-neck model can accurately replicate the experimental results and has the potential to be used as an efficient computational tool for brain and head injury biomechanics research.

Statements and Declarations

This work was primarily supported by the U.S. Department of Homeland Security (70RSAT21CB0000023). The MRI data acquisition was supported by the Texas Tech Neuroimaging Center.
Temperature and sex shape reproductive barriers in a climate change hotspot
Authors: Gallegos Cristóbal , Hodgins Kathryn A. , Monro Keyne
Published: February 2023

Climate change is shifting species ranges and altering reproductive interactions within those ranges, offering closely-related species new scope to mate and potentially hybridize. Predicting hybridization and its outcomes requires assessing the interplay of biological and climatic factors that mediate reproductive barriers across life stages. However, few studies have done so across the range of environments that parents and offspring potentially encounter in nature, as is crucial to understand the environmental sensitivity of reproductive isolation and its fate under climate change. We set out to assess prezygotic and postzygotic reproductive barriers, and their dependence on temperature and sex, in sister species of a marine tubeworm (Galeolaria) from a sentinel region for climate change impacts in southern Australia. We performed reciprocal crosses within- and between-species using replicate populations, and assessed fertility of crosses, survival of embryos, and survival of larvae, at five temperatures spanning the thermal ranges of populations in nature. We found that barriers were weak and independent of temperature at fertilization, but stronger and more temperature-sensitive at larval development, as species diverged in thermal tolerance. Barriers were asymmetric between reciprocal hybrids, moreover, suggesting a complex interplay between thermal adaptation in parental lineages and maternal inheritance of factors (e.g., mitochondria, endosymbionts) that influence hybrid viability across temperatures. Together, our findings provide new insights into the roles of temperature and sex in reproductive barriers across early life stages, and point to shifting strengths of reproductive isolation in future climates.
Completede novoassembly ofTricholoma bakamatsutakechromosomes revealed the structural divergence and differentiation ofTricholomagenomes
Authors: Ichida Hiroyuki , Murata Hitoshi , Hatakeyama Shin , Yamada Akiyoshi , Ohta Akira
Published: February 2023

Tricholoma bakamatsutake, which is an edible ectomycorrhizal fungus associated with Fagaceae trees, may have diverged before the other species inTricholomasectionCaligata. We generated a highly contiguous whole-genome sequence forT. bakamatsutakeSF-Tf05 isolated in an oak (Quercus salicina) forest in Japan. The assembly of high-fidelity long reads, with a median read length of 12.3 kb, resulted in 13 chromosome-sized contigs comprising 142,068,211 bases with an average GC content of 43.94%. The 13 chromosomes were predicted to encode 11,060 genes. A contig (122,566 bases) presumably containing the whole circular mitochondrial genome was also recovered. The chromosome-wide comparison ofT. bakamatsutakeandT. matsutake(TMA_r1.0) indicated that the basic number of chromosomes (13) was conserved, but the structures of the corresponding chromosomes diverged, with multiple inversions and translocations. Gene conservation and cluster analyses revealed at least three groups inTricholoma. Specifically, allT. bakamatsutakestrains belonged to the “bakamatsutake” clade, which is most proximal to the “caligatum” clade consisting ofT. caligatumandT. fulvocastaneum. The constructed highly contiguous telomere-to-telomere genome sequence of aT. bakamatsutakeisolate will serve as a fundamental resource for future research on the evolution and differentiation ofTricholomaspecies.
Apical extrusion prevents apoptosis from activating an acute inflammatory program in epithelia
Authors: Duszyc Kinga , von Pein Jessica B. , Ramnath Divya , Currin-Ross Denni , Verma Suzie , Lim Fayth , Sweet Matthew J. , Schroder Kate , Yap Alpha S.
Published: February 2023

Apoptosis is traditionally considered to be an immunologically silent form of cell death. Multiple mechanisms exist to ensure that apoptosis does not stimulate the immune system to cause inflammation or autoimmunity. Against this expectation, we now report epithelia are programmed to provoke, rather than suppress, inflammation in response to apoptosis. We found that an acute inflammatory response led by neutrophils occurs in zebrafish and cell culture when apoptotic epithelial cells cannot be expelled from the monolayer by apical extrusion. This reflects an intrinsic circuit where ATP released from apoptotic cells stimulates epithelial cells in the immediate vicinity to produce IL-8. As the epithelial barrier is compromised when apical extrusion fails, this juxta-apoptotic proinflammatory pathway may represent an early-response mechanism at sites of potential microbial ingress. Conversely, apical extrusion prevents inappropriate epithelial inflammation by physically eliminating apoptotic cells before they can activate this proinflammatory circuit.