bluuebunny/crossref_metadata_2025 huggingface dataset:
Health Impact Evaluation of Aspirational Districts Program in India: Evidence from National Family Health Survey
Authors: Agarwal Sandip K. , Mishra Shubham
Published: August 2023

The Aspirational District Program (ADP) is a unique initiative of Government of India launched in 2018 that aims to reduce inter-district multidimensional inequality. ADP aims to bring the most backward districts to catch up with the rest of the other districts in the country. The program is comprehensive in its scope as it targets the improvement of several key development indicators spanning health and nutrition, education, agriculture and water resources, financial inclusion and skill development and basic infrastructure indicators. Aspirational districts (ADs) are eligible for enhanced funding and priority allocation of various initiatives undertaken by the central and state governments. Our research estimates the causal impact of ADP on the targeted health and nutrition indicators using a combination of propensity score matching and difference-in-differences (PSM-DID). We use the fourth and fifth rounds of National Family Health Survey (NFHS) data collected in 2015-16 and 2019-21 respectively which serve as the pre and post-treatment data for our analysis. Moreover, we take advantage of the transparent mechanism outlined for the identification of ADs under ADP, which we use for propensity score matching for our PSM-DID. While we observe negative impact of ADP on early initiation of breastfeeding, we believe that the impact is confounded with the effects of Covid-19 since part of NFHS-5 data was collected during the pandemic. Therefore, the negative impact of ADP on early initiation of breastfeeding disappears when we only use pre-covid data. Additionally, using pre-covid data we find a reduction in the prevalence of underweight children younger than 5 years by 2 to 4% in ADs as an impact of ADP, which is robust across multiple specification. We do not find evidence of any other positive or negative impact of ADP on any other health and nutrition indicators, which is robust. Future research efforts should be made toward impact evaluation of all the targeted indicators in order to get a comprehensive unbiased evaluation of ADP.
Identification of Outcome-Oriented Progression Subtypes from Mild Cognitive Impairment to Alzheimer’s Disease Using Electronic Health Records
Authors: Xu Jie , Yin Rui , Huang Yu , Gao Hannah , Wu Yonghui , Guo Jingchuan , Smith Glenn E , DeKosky Steven T , Wang Fei , Guo Yi , Bian Jiang
Published: August 2023

Alzheimer’s disease (AD) is a complex heterogeneous neurodegenerative disease that requires an in-depth understanding of its progression pathways and contributing factors to develop effective risk stratification and prevention strategies. In this study, we proposed an outcome-oriented model to identify progression pathways from mild cognitive impairment (MCI) to AD using electronic health records (EHRs) from the OneFlorida+ Clinical Research Consortium. To achieve this, we employed the long short-term memory (LSTM) network to extract relevant information from the sequential records of each patient. The hierarchical agglomerative clustering was then applied to the learned representation to group patients based on their progression subtypes. Our approach identified multiple progression pathways, each of which represented distinct patterns of disease progression from MCI to AD. These pathways can serve as a valuable resource for researchers to understand the factors influencing AD progression and to develop personalized interventions to delay or prevent the onset of the disease.
Predicting Long COVID in the National COVID Cohort Collaborative Using Super Learner
Authors: Butzin-Dozier Zachary , Ji Yunwen , Li Haodong , Coyle Jeremy , Shi Junming (Seraphina) , Philips Rachael V. , Mertens Andrew , Pirracchio Romain , van der Laan Mark J. , Patel Rena , Colford John M. , Hubbard Alan E.
Published: August 2023

Post-acute Sequelae of COVID-19 (PASC), also known as Long COVID, is a broad grouping of a range of long-term symptoms following acute COVID-19 infection. An understanding of characteristics that are predictive of future PASC is valuable, as this can inform the identification of high-risk individuals and future preventative efforts. However, current knowledge regarding PASC risk factors is limited. Using a sample of 55,257 participants from the National COVID Cohort Collaborative, as part of the NIH Long COVID Computational Challenge, we sought to predict individual risk of PASC diagnosis from a curated set of clinically informed covariates. We predicted individual PASC status, given covariate information, using Super Learner (an ensemble machine learning algorithm also known as stacking) to learn the optimal, AUC-maximizing combination of gradient boosting and random forest algorithms. We were able to predict individual PASC diagnoses accurately (AUC 0.947). Temporally, we found that baseline characteristics were most predictive of future PASC diagnosis, compared with characteristics immediately before, during, or after COVID-19 infection. This finding supports the hypothesis that clinicians may be able to accurately assess the risk of PASC in patients prior to acute COVID diagnosis, which could improve early interventions and preventive care. We found that medical utilization, demographics, anthropometry, and respiratory factors were most predictive of PASC diagnosis. This highlights the importance of respiratory characteristics in PASC risk assessment. The methods outlined here provide an open-source, applied example of using Super Learner to predict PASC status using electronic health record data, which can be replicated across a variety of settings.
Variety of Energy-Dense Foods Does Not Affect Body Mass Index but Influences Food Quantity: Evidence from a Cross-Sectional Study among Adolescents in Mumbai, India
Authors: Dawoodani Elina , Gokhale Chanda
Published: August 2023

Introduction

Over the past three decades, adolescents’ share of caloric consumption from foods that are energy-dense but low in micronutrients has increased dramatically. Additionally, the rise in overweight and obesity in this age group is one of the most significant public health challenges of recent times.

Objective

We intended to investigate the relationship between consuming a variety of energy-dense foods and body mass index in adolescents.

Research Methods and Procedures

In this analytical cross-sectional study, 373 adolescents between the age of 13-15 years old were randomly recruited from three private schools in Mumbai, India. Data on their weekly consumption of energy-dense foods, anthropometric measurements, along with other critical information was obtained using a survey and food frequency questionnaire. Categories of energy-dense foods considered included chat (Indian savory snack) and street foods, appetizers, main course, continental foods, aerated drinks, baked foods, Indian sweets, farsan (fried Indian snack), and packaged foods.

Results

Amongst the participants (n =373, mean age 13.4 years), 39.7% were underweight, 46.1% had a normal BMI, 9.6% were overweight, and 4.5% were obese. They reported consuming an average of 4 varieties and 10.6 servings of energy-dense foods a day. Though the consumption of a variety of energy-dense foods was not found to be associated with body mass index, it was found to be significantly, positively, and strongly associated with the number of servings consumed, indicating that variety does increase total food consumption.

Conclusion

In this cohort of adolescents, overall consumption of a variety of energy-dense foods does not seem to influence body mass index. Longitudinal studies are warranted to assess the impact of variety on total body composition.
Fluoroscopy time as a new predictor of short-term outcomes after transcatheter aortic valve replacement
Authors: Cafaro Alessandro , Spione Francesco , Burattini Osvaldo , Feo Daniele De , Xhelo Alessandro , Palmitessa Chiara , D’Alessandro Maurizio , Amendola Vincenzo Pio , Rimmaudo Flavio , Guaricci Andrea Igoren , Bortone Alessandro Santo , Pestrichella Vincenzo , Contegiacomo Gaetano , Tesorio Tullio , Colonna Giuseppe , Iacovelli Fortunato
Published: August 2023

Objective

Transcatheter aortic valve replacement (TAVR) is a cine-fluoroscopic guided procedure. The amount of radiation used during the procedure is strictly related with fluoroscopy time (FT) that has been demonstrated to be associated with outcomes and complexity of procedure in percutaneous coronary interventions. The aim of our study is to demonstrate the relationship between FT and short-term outcomes after TAVR.

Methods

After splitting 1797 consecutive patients according to tertiles of FT, the composite endpoint early safety (ES) was adjudicated according to Valve Academic Research Consortium (VARC)-2 and -3 consensus documents and the composite endpoints of device success (DS) and technical success (TS) according to VARC-3 criteria.

Results

The absence of all outcomes (TS, DS, and ES according to VARC-3 and ES according to VARC-2) was significantly associated with higher FT and this association persisted after propensity score matching analysis. Notwithstanding, after receiver operating characteristic analysis, only the FT cut-offs identified for VARC-3 TS and VARC-2 ES had adequate diagnostic accuracy in identifying the absence of these endpoints.

Conclusions

Longer FT is related with peri-procedural and short-term outcomes after the procedure, especially in those that are more complex. A FT duration of more than 30 minutes has an adequate accuracy in identifying VARC-3 technical failure and absence of VARC-2 ES.

What is already known on this topic

FT is related with complexity and outcomes in PCI. No data is available about FT and TAVR.

What this study adds

FT >30 minutes has an adequate accuracy in identifying VARC-3 technical failure and absence of VARC-2 ES.

How this study might affect research, practice or policy

FT that lasts more than 30 minutes in TAVR is linked independently to short-term adverse outcomes after TAVR. A strict follow-up is needed in this procedural setting as FT is a new independent predictor of adverse outcome after TAVR.
Genome-wide DNA methylation-analysis delineates blastic plasmacytoid dendritic cell neoplasm from related entities and identifies distinct molecular features
Authors: Künstner Axel , Schwarting Julian , Witte Hanno M. , Xing Pengwei , Bernard Veronica , Stölting Stephanie , Lohneis Philipp , Janke Florian , Salehi Maede , Chen Xingqi , Kusch Kathrin , Sültmann Holger , Chteinberg Emil , Fischer Anja , Siebert Reiner , von Bubnoff Nikolas , Merz Hartmut , Busch Hauke , Feller Alfred C. , Gebauer Niklas
Published: August 2023

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) constitutes a rare and aggressive malignancy originating from plasmacytoid/common dendritic cells (pDCs/cDCs) with a primarily cutaneous tropism followed by dissemination to the bone marrow and other organs. We conducted a genome-wide analysis of the tumor methylome in an extended cohort of 45 BPDCN patients supplemented by WES (n=54) and RNA-seq (n=54) as well as ATAC-seq on selected cases (n=4). We determine the BPDCN DNA methylation profile and thereby identify a reliable means to discriminate BPDCN from AML, CMML and T-ALL. DNA methylation profiling characterizes disruption of oncogenic pathways whilst unraveling the proliferative history as well as the prognostically relevant composition of the tumor microenvironment. Beyond the two recently established BPDCN subtypes (C1/C2), we identified a transcriptional reliance on JAK/STAT and NFκB-signaling in atypical C2 versus C1-BPDCN cases through RNA-sequencing. Our integrative characterization of BPDCN offers novel molecular insights and potential diagnostic applications.
How Often Do Patients Need Retreatment After Surgery for Subdural Hematoma? A Nationwide Readmission Database Analysis
Authors: Nazari Pouya , Golnari Pedram , Metcalf-Doetsch William Nathaniel , Potts Matthew B. , Jahromi Babak S.
Published: August 2023

Background and purpose

The incidence of subdural hematoma (SDH) is increasing as the average age in the US rises, with reported high recurrence and reoperation rates. We therefore aimed to have a better understanding of retreatment following surgical evacuation of SDH in real-world practice.

Methods

Data were extracted from the latest available Nationwide Readmissions Database (2016-2019). Adult patients diagnosed with SDH who had burr-hole or craniotomy were included in the study.

Results

Retreatment rates were relatively low in both cohorts, with patients in the burr-hole cohort having a slightly higher rate of retreatment compared to the craniotomy cohort (8.4% vs 6.6%, p<0.001). The majority (>95%) of retreatments occurred within 90 days of initial treatment, and further follow up did not demonstrably increase retreatment on Kaplan Meier analysis. Retreatment rates remained consistent during the four-year study period in both burr-hole (7.2%-10.4%), and craniotomy cohorts (6.4%-6.8%).

Conclusions

Analysis of a large national database of unselected patients shows retreatment rates after surgery for SDH are lower than suggested by prior studies. Almost all retreatments occur within 90 days after initial treatment, which may have implications for length of follow up for such patients.
CLINICAL AND SEROLOGICAL PREDICTORS OF POST COVID-19 CONDITION – FINDINGS FROM A CANADIAN PROSPECTIVE COHORT STUDY
Authors: Collins Erin , Galipeau Yannick , Arnold Corey , Bhéreur Anne , Booth Ronald , Buchan Arianne C. , Cooper Curtis , Crawley Angela M. , McCluskie Pauline S. , McGuinty Michaeline , Pelchat Martin , Rocheleau Lynda , Saginur Raphael , Gravel Chris , Hawken Steven , Langlois Marc-André , Little Julian
Published: August 2023

Introduction

More than three years into the pandemic, there is persisting uncertainty as to the etiology, biomarkers, and risk factors of Post COVID-19 Condition (PCC). Serological research data remain a largely untapped resource. Few studies have investigated the potential relationships between post-acute serology and PCC, while accounting for clinical covariates.

Methods

We compared clinical and serological predictors among COVID-19 survivors with (n=102 cases) and without (n=122 controls) persistent symptoms ≥12 weeks post-infection. We selected four primary serological predictors (anti-nucleocapsid (N), anti-Spike, and anti-receptor binding domain (RBD) IgG titres, and neutralization efficiency), and specified clinical covariates a priori.

Results

Similar proportions of PCC-cases (66.7%, n=68) and infected-controls (71.3%, n=87) tested positive for anti-N IgG. More cases tested positive for anti-Spike (94.1%, n=96) and anti-RBD (95.1%, n=97) IgG, as compared with controls (anti-Spike: 89.3%, n=109; anti-RBD: 84.4%, n=103). Similar trends were observed among unvaccinated participants. Effects of IgG titres on PCC status were non-significant in univariate and multivariate analyses. Adjusting for age and sex, PCC-cases were more likely to be efficient neutralizers (OR 2.2, 95% CI 1.11 – 4.49), and odds was further increased among cases to report deterioration in quality of life (OR 3.4, 95% CI 1.64 – 7.31). Clinical covariates found to be significantly related to PCC included obesity (OR 2.3, p=0.02), number of months post COVID-19 (OR 1.1, p<0.01), allergies (OR 1.8, p=0.04), and need for medical support (OR 4.1, p<0.01).

Conclusion

Despite past COVID-19 infection, approximately one third of PCC-cases and infected-controls were seronegative for anti-N IgG. Findings suggest higher neutralization efficiency among cases as compared with controls, and that this relationship is stronger among cases with more severe PCC. Cases also required more medical support for COVID-19 symptoms, and described complex, ongoing health sequelae. More data from larger cohorts are needed to substantiate results, permit subgroup analyses of IgG titres, and explore for differences between clusters of PCC symptoms. Future assessment of IgG subtypes may also elucidate new findings.
Feasibility of a high-dose behavioural exercise intervention on upper limb motor function in chronic stroke survivors
Authors: van der Groen Onno , Garcia-Vega Jimena , van Rijn Kirsten , Edwards Dylan
Published: August 2023

Background

Stroke is a leading cause of adult disability and high-dose interventions may help reduce it. However, current practice does not allow for this.

Purpose

This study tests the feasibility of a high-dose upper limb therapy in chronic stroke survivors using a neuroanimation therapy (NAT).

Methods

Four chronic stroke survivors underwent 20 NAT sessions, 3 or 5 times a week for 90 minutes time-on-task. Feasibility was assessed with compliance to number of sessions and total time-on-task. Secondary outcomes included Fugle-Meyer Upper Extremity motor score (FM-UE), Action Research Arm Test (ARAT), grip strength, movement kinematics and cognition assessed using robotic technology.

Results

All participants attended the 20 prescribed sessions on the 3-day per week schedule. Two completed 90 minutes time-on-task in all sessions. Two showed clinical improvements in their FM-UE and ARAT. Movement kinematic analysis demonstrated improvements in motor control and cognition, however these changes did not seem to last when re-tested 1 month after the last training session.

Conclusion

20 sessions of NAT is feasible in the chronic phase of stroke recovery with a 3-day per week schedule. Clinical improvements in arm function were observed in this high-dose upper limb NAT therapy, in one mild and one moderately affected stroke survivor.
Automated artifact injection into sensing-capable brain modulation devices for neural-behavioral synchronization and the influence of device state
Authors: Alarie Michaela E , Provenza Nicole R , Herron Jeffrey A , Asaad Wael F
Published: August 2023

Background

Sensing-enabled deep brain stimulation (DBS) devices enable opportunities to investigate correlations between neural activity and behavior. Unfortunately, these devices do not allow straightforward synchronization of neural data with external events.

Objective

To implement and assess an automated neural-behavioral synchronization system for a fully implanted DBS system.

Methods and Results

We describe a synchronization strategy that relies on computer-driven artifact injection via event-triggered transcutaneous stimulation (TS). We validated the temporal accuracy of the approach in two patients receiving DBS for treatment of Parkinson’s disease, observing consistently low jitter between task events and subsequent TS artifacts during DBS OFF (± 22.9ms) and ON (± 9.08ms) conditions. Notably, we observed that event-triggered TS was modulated by device state, where active circuitry during specific streaming modes influenced artifact injection in the data.

Conclusion

We describe a rigorous approach for neural-behavioral alignment using fully implanted DBS systems and demonstrate how accuracy of alignment depends on device state.
Exploring Disparities and Novel Insights into Metabo-Nutritional Comorbidities among COVID-19 Patients in Mexico
Authors: López-Cuevas Ariel , Martínez-García Mireya , Hernández-Lemus Enrique , de Anda-Jáuregui Guillermo
Published: August 2023

During the previous years, particularly at the beginning of the COVID-19 pandemic, the potential role of metabo-nutritional comorbidities in the severity and lethality of SARS-CoV2 infection has been widely discussed, often describing ambiguous outcomes. Here we investigate the prevalence of metabo-nutritional comorbidities among COVID-19 patients in Mexico. Using a retrospective observational study design, data was collected from official databases of COVID-19 patients admitted to public and private hospitals in Mexico City. Our study found a discordant prevalence of metabo-nutritional comorbidities among COVID-19 patients, particularly obesity, hypertension, and diabetes. Discordance consists in geographic location-dependent over and under-representation phenomena, that is the prevalence of such comorbidities in COVID-19 patients was significantly over or under the reported value for the general population in each location. These findings highlight the importance of screening for metabo-nutritional comorbidities in COVID-19 patients and suggest the need for tailored interventions for this population. The study also provides insights into the complex relationships between COVID-19 and metabo-nutritional comorbidities, which may inform future research and clinical practice.
Do we need to reconsider knee valgus as a sole risk factor for second ACL injury? Exploratory analysis of individual Landing Error Scoring System (LESS) items with three year follow-up
Authors: van Melick Nicky , van Rijn Lisa , Bogie Rob , Hoogeboom Thomas J.
Published: August 2023

Background

It remains unclear which movement quality items are associated with second anterior cruciate ligament (ACL) injuries after ACL reconstruction.

Hypotheses

1) Movement quality measured with the Landing Error Scoring System (LESS) is not associated with second ACL injury in soccer players who returned to sports after ACL reconstruction. 2) In an exploratory analysis, soccer players with and without second ACL injuries display differences in individual LESS items.

Methods

Fourteen male recreational ACL-reconstructed soccer players had non-fatigued and fatigued movement quality measurement with LESS score three years ago and were now interviewed by phone about soccer participation and second ACL injuries.

Results

Two soccer players did not return to soccer and were therefore excluded from analysis. Six of twelve (50%) included soccer players had a second ACL injury. There was no association between the non-fatigued (p=1.000) and fatigued (p=0.455) LESS score and second ACL injuries. However, when exploring individual LESS items, we found 50% of the soccer players with second ACL injury landing with little trunk and knee flexion displacement in combination with knee valgus, while none of the soccer players without second ACL injury had this combination of LESS errors. This difference was only seen in the fatigued state.

Conclusions

It might be the combination of little knee and trunk flexion displacement with knee valgus during landing which predisposes an athlete to a second ACL injury, especially in a fatigued state.

Clinical relevance

When screening athletes after ACL reconstruction for second ACL injury risk, combining measurement of knee valgus with knee and trunk flexion displacement in a fatigued state might be give more insight into risk than using the complete LESS score or evaluating knee valgus as a sole risk factor.
The impact of intracranial pressure telesensors: an observational propensity matched-control analysis of service demand and costs
Authors: Pandit Anand S , Kamal Muhammad A , Reischer Gerda , Aldabbagh Yousif , Alradhawi Mohammad , Lee Faith MY , Sekhon Priya P , Moncur Eleanor M , Banks Ptolemy DW , Thompson Simon , Thorne Lewis , Watkins Laurence D , Toma Ahmed K
Published: August 2023

Background: Implantable telemetric intracranial pressure sensors (telesensors) enable routine, non-invasive ICP feedback, aiding clinical decision-making and attribution of pressure-related symptoms in patients with CSF shunt systems. Here, we aim to explore the impact of these devices on service demand and costs in patients with adult hydrocephalus. Methods: We performed an observational propensity matched control study, comparing all patients who had an MScio/Sensor Reservoir (Christoph Mietke, GmbH & Co) against those with a non-telemetric reservoir between March 2016 and March 2018. Patients were matched based on demographics, diagnosis, shunt-type and revision status. Neurosurgical service usage was recorded with frequencies of neurosurgical admissions, outpatient clinics, scans and further surgical procedures in the two years prior and after shunt insertion. Results: 136 patients: 73 telesensor and 63 controls were included in this study (48 matched pairs). Telesensor use led to a significant decrease in neurosurgical inpatient admissions, radiographic encounters and further procedures such as intracranial pressure monitoring. After multivariate adjustment, the mean cumulative saving after two years was 5236 GBP (6338 USD) in telesensor patients (5498 GBP on matched pair analysis). On break-even analysis, cost-savings were likely to be achieved within 8 months of clinical use, post-implantation. Telesensor patients also experienced a significant reduction in imaging-associated radiation (4 mSv) over two years. Conclusions: The findings of this exploratory study reveal that telesensor implantation is associated with reduced service demand and provides net financial savings from an institutional perspective. Moreover, telesensor patients required fewer appointments, invasive procedures, and had less radiation exposure, indicating an improvement in both their experience and safety.
Treatment practice of vasospasm during endovascular thrombectomy: an international survey
Authors: Jesser J. , Nguyen T. N. , Dmytriw A. A. , Yamagami H. , Miao Z. , Sommer L. J. , Stockero A. , Pfaff J. A. R. , Ospel J. M. , Goyal M. , Patel A. B. , Mendes Pereira V. , Hanning U. , Meyer L. , van Zwam W. , Bendszus M. , Wiesmann M. , Möhlenbruch M. A. , Weyland C. S.
Published: August 2023

Background and aim

The clinical importance and management of vasospasm as a complication during endovascular stroke treatment (EVT) has not been well studied. We sought to investigate current expert opinions in neuro-intervention and therapeutic strategies of iatrogenic vasospasm during EVT.

Methods

We conducted an anonymous international online survey (April 04thto May 15th2023) addressing treatment standards of neurointerventionalists (NI) practicing EVT. Several illustrative cases of patients with vasospasm during EVT were shown. Two study groups were compared according to the NI’s opinion regarding the potential influence of vasospasm on patient outcome after EVT using descriptive analysis.

Results

In total, 534 NI from 56 countries responded, of whom 51.5% had performed more than 200 EVT. Vasospasm was considered a complication potentially influencing the patient’s outcome by 52.6% (Group 1) whereas 47.4% did not (Group 2). Physicians in Group 1 more often added vasodilators to their catheter flushes during EVT routinely (43.7% vs. 33.9%, p = 0.033) and more often treated severe large-vessel vasospasm with vasodilators (75.3% vs. 55.9%; p < 0.001), as well as extracranial vasospasm (61.4% vs. 36.5%, p < 0.001) and intracranial medium-vessel vasospasm (27.1 % vs. 11.2%, p < 0.001), compared to Group 2. In case of a large-vessel vasospasm and residual and amenable medium vessel occlusion during EVT, the study groups showed different treatment strategies. Group 2 continued the EVT immediately more often, without initiating therapy to treat the vasospasm first (9.6% vs 21.1%, p < 0.001).

Conclusion

There is disagreement among neurointerventionalists about the clinical relevance of vasospasm during EVT and its management. There was a higher likelihood of use of preventive and active vasodilator treatment in the group that perceived vasospasm as a relevant complication as well as differing interventional strategies for continuing an EVT in the presence of a large-vessel vasospasm.
Frequency-dependent selection of neoantigens fosters tumor immune escape and predicts immunotherapy response
Authors: Chen Shaoqing , Xie Duo , Wang Jiguang , Hu Zheng , Zhou Da
Published: August 2023

Cancer is an evolutionary process undergoing stringent immune selection. However, recent studies have revealed that certain tumors undergo neutral evolution following the malignant transformation. Here, we propose negative frequency-dependent selection (or NFDS), where the immune response against cancer cells depends on the clonality of neoantigens, can lead to an immunogenic landscape that is similar to neutral evolution. With a stochastic model of NFDS, we demonstrated that NFDS promotes early immune evasion in hypermutable tumors, leading to neutral-like evolutionary dynamics with high antigenic heterogeneity and worse response to immune checkpoint blockade (ICB) therapy. Our model also revealed that NFDS is characterized by a negative association between average clonality and total burden of neoantigens. Indeed, NFDS was validated with whole-exome sequencing datasets (357 tumor samples from 275 patients) from four melanoma cohorts with ICB therapy. Altogether, our study provides the first quantitative evidence supporting the theory of NFDS in immune-driven cancer evolution. These findings highlight the critical role of NFDS theory in devising more efficient and predictive immunotherapies.
Distinct roles of putative excitatory and inhibitory neurons in the macaque inferior temporal cortex in core object recognition behavior
Authors: Sanghavi Sachi , Kar Kohitij
Published: August 2023

A spatially distributed population of neurons in the macaque inferior temporal (IT) cortex supports object recognition behavior, but the cell-type specificity of the population in forming “behaviorally sufficient” object decodes remain unclear. To address this, we recorded neural signals from the macaque IT cortex and compared the object identity information and the alignment of decoding strategies derived from putative inhibitory (Inh) and excitatory (Exc) neurons to the monkeys’ behavior. We observed that while Inh neurons represented significant category information, decoding strategies based on Exc neural population activity outperformed those from Inh neurons in overall accuracy and their image-level match to the monkeys’ behavioral reports. Interestingly, both Exc and Inh responses explained a fraction of unique variance of the monkeys’ behavior, demonstrating a distinct role of the two cell types in generating object identity solutions for a downstream readout. We observed that current artificial neural network (ANN) models of primate ventral stream, designed with AI goals of performance optimization on image categorization, better predict Exc neurons (and its contribution to object recognition behavior) than Inh neurons. Beyond, the refinement of linking propositions between IT and object recognition behavior, our results guide the development of more biologically constrained brain models by offering novel cell-type specific neural benchmarks.
Exome-wide association study reveals 7 functional variants associated with ex-vivo drug response in acute myeloid leukemia patients
Authors: Giri Anil K , Lin Jake , Kyriakidis Konstantinos , Tripathi Garima , Almusa Henrikki
Published: August 2023

Acute myeloid leukemia (AML) is a rare aggressive blood cancer without any long-term cure. Further, due to the extreme molecular heterogeneity of the disease, drug treatment response varies from patient to patient. The variability of drug response can cause unnecessary treatment in more than half of the patients with no or partial therapy responses leading to severe side effects, economic as well as time loss. Understanding the genetic risk factors underlying the drug response in AML can help with improved prediction of treatment responses and identification of biomarkers in addition to mechanistic insights to monitor treatment response.

Here, we report the results of the largest exome-wide association study (EWAS) of ex-vivo drug response performed to date with 175 AML cases and 47 drugs. We used information from 55423 exonic SNPs to perform the analysis. We identified exome-wide significant (p<9.02 ×10-7) associations for rs113985677 inCCINwith tamoxifen response, rs115400838 inTRMT5with idelalisib response, rs11878277 inHDGFL2with entinostat, and rs2229092 in LTA associated with vorinostat response.

Further, using multivariate genome-wide association analysis, we identified the association of rs11556165 inATRAID, and rs11236938 inTSKUwith the combined response of all 47 drugs and 29 nonchemotherapy drugs at the genome-wide significance level (p<5×10-8). Additionally, a significant association of rs35704242 inNIBAN1was associated with the combined response for nonchemotherapy medicines (p=2.51×10-8), and BI.2536, gefitinib, and belinostat were identified as the central traits. Our study represents the largest EWAS study to date on ex-vivo drug response in AML and reports 7 new associated loci that help to understand the anticancer drug response in AML patients.
Impact of γ-herpes viruses’ status on established risk factor profile of oral squamous cell carcinoma tissues in a group of Sri Lankan male
Authors: Perera Manosha Lakmali , Perera Irosha Rukmali
Published: August 2023

Oral cancer with multifactorial aetiology was established as a public health challenge globally especially locally. Alarmingly, oral cancer ranks 1st among Sri Lankan males and 8thamong Sri Lankan females with 2-3 death daily. Oral squamous cell carcinoma (OSCC) accounts for 90-95% of oral malignancies in most countries. Perhaps, infectious agents are responsible for approximately 20% of global cancer incidence. Among them, Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpes virus (KHSV) are γ-herpes viruses linked with mucosal malignancies also. There is a dearth of information on oncogenic viral infections in oral cancer patients. Thus, the present study aimed to investigate the impact of γ-herpes viruses’ status on the -established risk factor profile of OSCC tissue in a group of Sri Lankan male patients. Ethical approvals were obtained from Sri Lanka and Australia. A large unmatched case-control study was conducted on Oral and Maxillo-Facial Surgical (OMF) units located in six provinces. Consequently, a representative sub-sample of histopathologically confirmed 29 OSCC cases and clinically diagnosed 25 Fibroepithelial-poly (FEP)controls was selected from the main, adhering to stringent inclusion criteria, for cases at least with betel quid chewing, while excluding none of oral risk habits. Incisional biopsies of cases and excisional biopsies of controls were collected, transported, stored, and dispatched as frozen tissues at - 800C. Then, DNA was extracted from frozen specimens. Subsequently, real-time PCR was performed to detect γ-herpes viruses separately. Socio demographic and clinical data were obtained entered and analysed using SPSS-21 Statistical Package. Descriptive statistics and Fisher’s exact test were used to compare groups ((cell counts <5). The overall EBV prevalence was calculated as 34 (64.2%). In OSCC cases the EBV positivity was higher 21(77.8%) than the FEP controls 13 (50.0%), and this difference was statistically significant (p<0.05). Neither cases nor controls infected with KSHV/HHV-8. In oral risk habit comparison, the cases were better substance abusers, especially in terms of betel quid chewing and alcohol consumption than the control group (p<0.05), The impacts of γ-herpes viruses’ status on established risk factors are noteworthy to investigate by adequately powered prospective studies exclusively in local and regional context.
Effect of an intensive lifestyle intervention on the structural and functional substrate for atrial fibrillation in people with metabolic syndrome
Authors: Rossello Xavier , Ramallal Raúl , Romaguera Dora , Alonso-Gómez Ángel M. , Alonso Alvaro , Tojal-Sierra Lucas , Fernández-Palomeque Carlos , Martínez-González Miguel Ángel , Garrido-Uriarte María , López Luis , Díaz Agnes , Zaldua-Irastorza Olatz , Shah Amit J. , Salas-Salvadó Jordi , Fitó Montserrat , Toledo Estefania
Published: August 2023

Aims

To evaluate the effect of an intensive lifestyle intervention (ILI) on the structural and functional cardiac substrate of atrial fibrillation (AF) in overweight or obese people with metabolic syndrome (MetS).

Methods

Participants of the PREDIMED-PLUS trial (n=6874) were randomised 1:1 to an ILI program based on an energy-reduced Mediterranean diet, increased physical activity, and cognitive-behavioural weight management, or to a control intervention of low-intensity dietary advice. Left atrial (LA) strain, function, and volumes were evaluated by a core echocardiography lab in 534 participants at baseline, 3-year and 5-year follow-up. Mixed models were used to evaluate the effect of the ILI on LA structure and function.

Results

In the subsample, baseline mean age was 65 years (SD 5 years), and 40% of the participants were women. Over the 5-year period, both groups experienced worsening of LA structure and function, with increases in LA volumes and stiffness index and decreases in LA longitudinal strain, LA function index and LA emptying fraction over time. Changes in the ILI and control group were not significantly different for any of the primary outcomes (LA emptying fraction: -0.95% (95%CI -0.93, -0.98) in control group, -0.97% (95%CI -0.94, -1.00) in ILI group, pbetween groups=0.80; LA longitudinal strain: 0.82% (95%CI 0.79, 0.85) in control group, 0.85% (95%CI 0.82, 0.89) in ILI group, pbetween groups=0.24) or any of the secondary outcomes.

Conclusions

In overweight or obese people with MetS, an ILI had no impact on the underlying structural and functional left atrial substrate measurements associated with AF risk.
Estimation of the direct health costs attributable to child obesity in Brazil
Authors: Nilson Eduardo Augusto Fernandes , da Costa Michele Gonçalves , Rocha Carolina , Honorio Olivia , Barreto Raphael
Published: August 2023

Introduction

Childhood obesity is a major global public health issue globally and in Brazil. The impacts of childhood obesity include higher risk of disease during childhood and of obesity and non-communicable diseases in adulthood and represent an important epidemiological and economic burden to countries.

Methods

This study is based on the modeling of total costs of hospitalizations and the additional costs attributable to childhood obesity in the Brazilian National Health System.

Results

The hospitalizations of children and adolescents with obesity as a primary cause totaled R$5.5 million to the Brazilian National Health System from 2013 to 2022, demonstrating that obesity is rarely considered as a cause of hospitalization especially among children and adolescents. The additional costs of hospitalizations attributable to childhood obesity totaled R$213.1 million during the same period. Considering the additional non-hospital, outpatient and medication cost attributable to childhood obesity in Brazil, the total costs were estimated at R$225.7 million in the last decade.

Conclusion

This study highlight that the costs of childhood obesity are not limited to the impacts on adult health and represent a relevant economic burden to the Brazilian National Health System and to families because of additional costs during childhood. Therefore, the prevention and control of childhood obesity is a public health priority that demands immediate and robust policies.
Post-acute health care costs following SARS-CoV-2 infection: A retrospective cohort study of among 531,182 matched adults
Authors: McNaughton Candace D. , Austin Peter C. , Li Zhiyin , Sivaswamy Atul , Fang Jiming , Abdel-Qadir Husam , Udell Jacob A. , Wodchis Walter , Lee Douglas S. , Mostarac Ivona , Atzema Clare L.
Published: August 2023

Post-acute health care costs following SARS-CoV-2 infection are not known. Beginning 56 days following SARS-CoV-2 polymerase chain reaction (PCR) testing, we compared person-specific total and component health care costs across their distribution for the following year (test-positive versus test-negative, matched people; January 1, 2020-March 31, 2021). For 531,182 individuals, mean person-specific total health care costs were $513.83 (95% CI $387.37-$638.40) higher for test-positive females and $459.10 (95% CI $304.60-$615.32) higher for test-positive males, or >10% increase in mean per-capita costs, driven by hospitalization, long-term care, and complex continuing care costs. At the 99thpercentile of each subgroup, person-specific health care costs were $12,533.00 (95% CI $9,008.50-$16,473.00) higher for test-positive females and $14,604.00 (95% CI $9,565.50-$19,506.50) for test-positive males, driven by hospitalization, specialist (males), and homecare costs (females). Cancer costs were lower. Six-month and 1-year costs differences were similar. These findings can inform planning for post-acute SARS-CoV-2 health care costs.
Improving Genetic Association Studies with a Novel Methodology that Unveils the Hidden Complexity of All-Cause Heart Failure
Authors: Gregg John T. , Himes Blanca E. , Asselbergs Folkert W. , Moore Jason H.
Published: August 2023

Motivation

Genome-Wide Association Studies (GWAS) commonly assume phenotypic and genetic homogeneity that is not present in complex conditions. We designed Transformative Regression Analysis of Combined Effects (TRACE), a GWAS methodology that better accounts for clinical phenotype heterogeneity and identifies gene-by-environment (GxE) interactions. We demonstrated with UK Biobank (UKB) data that TRACE increased the variance explained in All-Cause Heart Failure (AHF) via the discovery of novel single nucleotide polymorphism (SNP) and SNP-by-environment (i.e. GxE) interaction associations. First, we transformed 312 AHF-related ICD10 codes (including AHF) into continuous low-dimensional features (i.e., latent phenotypes) for a more nuanced disease representation. Then, we ran a standard GWAS on our latent phenotypes to discover main effects and identified GxE interactions with target encoding. Genes near associated SNPs subsequently underwent enrichment analysis to explore potential functional mechanisms underlying associations. Latent phenotypes were regressed against their SNP hits and the estimated latent phenotype values were used to measure the amount of AHF variance explained.

Results

Our method identified over 100 main GWAS effects that were consistent with prior studies and hundreds of novel gene-by-smoking interactions, which collectively accounted for approximately 10% of AHF variance. This represents an improvement over traditional GWAS whose results account for a negligible proportion of AHF variance. Enrichment analyses suggested that hundreds of miRNAs mediated the SNP effect on various AHF-related biological pathways. The TRACE framework can be applied to decode the genetics of other complex diseases.

Availability

All code is available athttps://github.com/EpistasisLab/latent_phenotype_project
Discovery of a multipotent cell type from the term human placenta
Authors: Vadakke-Madathil Sangeetha , Bouhamida Esmaa , Wang Bingyan J , Mathiyalagan Prabhu , Oniskey Micayla , Santos-Gallegos Carlos , Hadley Michael , Croft Lori , Dekio Fumiko , Brody Rachel , Gelber Shari , Sperling Rhoda , Chaudhry Hina W.
Published: August 2023

We report a population of multipotent cells isolated from term human placentas, for the first time, that differentiates into cardiomyocytes and vascular cells with clonal ability, migratory ability, and trancriptomic evidence of immune privilege. Caudal-type homeobox-2 (CDX2) is a conserved factor that regulates trophectoderm formation and placentation during early embryonic development but has not previously been implicated in developmentally conserved regenerative mechanisms. We earlier reported that murine Cdx2 cells restored cardiac function after intravenous delivery in male mice with experimental myocardial infarction (MI). Here we demonstrate that CDX2 cells found in human chorion are poised for cardiovascular differentiation. We isolated CDX2 cells from term placentas of 150 healthy patients and showed that they spontaneously differentiate into cardiomyocytes, functional vascular cells, and retain homing abilityin vitrowith a transcriptome that supports enhanced cardiogenesis, vasculogenesis, immune modulation, and chemotaxis gene signatures. They restore cardiac function when administered to NOD/SCID mice subjected to MI. CDX2 cells can be clonally propagated in culture with retention of cardiovascular differentiation. Our data compels further use of this ethically feasible cell source in the design of therapeutic strategies for cardiovascular disease.

One-sentence Summary

CDX2 cells from human placenta are poised for cardiovascular differentiation and may lead to a novel therapeutic approach for human heart repair.
Chrombus-XMBD: A Graph Generative Model Predicting 3D-Genome,ab initiofrom Chromatin Features
Authors: Zeng Yuanyuan , You Zhiyu , Guo Jiayang , Zhao Jialin , Zhou Ying , Huang Jialiang , Lyu Xiaowen , Chen Longbiao , Li Qiyuan
Published: August 2023

Abstracts

The landscape of 3D-genome is crucial for transcription regulation. But capturing the dynamics of chromatin conformation is costly and technically challenging. Here we described “Chrombus-XMBD”, a graph generative model capable of predicting chromatin interactionsab initobased on available chromatin features. Chrombus employes dynamic edge convolution with QKV attention setup, which maps the relevant chromatin features to a learnable embedding space thereby generate genomewide 3D-contactmap. We validated Chrombus predictions with published databases of topological associated domains (TAD), eQTLs and gene-enhancer interactions. Chrombus outperforms existing algorithms in efficiently predicting long-range chromatin interactions. Chrombus also exhibits strong generalizability across different cell lineage and species. Additionally, the parameter sets of Chrombus inform the biological processes underlying 3D-genome. Our model provides a new perspective towards interpretable AI-modeling of the dynamics of chromatin interactions and better understanding ofcis-regulation of gene expression.
Biogenic phosphonate utilization by globally distributed diatomThalassiosira
Authors: Shu Huilin , Shen Yuan , Wang Hongwei , Sun Xueqiong , Ma Jian , Lin Xin
Published: August 2023

Phosphonate is a class of enigmatic organic phosphorus compounds that contribute ∼25% of total dissolved organic phosphorus (DOP). Recent studies reveal the important role of phosphonate mediated by prokaryotes in the marine P redox cycle, however, its bioavailability and metabolic process by eukaryotic phytoplankton are under debate. 2-Aminoethylphosphonic acid and (2-AEP) and 2-amino-3-phosphonopropionic acid (2-AP3) are two biogenic phosphonates that ubiquitously exist in marine environment. Here, we report thatThalassiosira pseudonana, a dominant diatom species in the ocean, are able to recover growth from phosphorus starvation with individual supplement of 2-AEP and 2-AP3. Moreover, the cellular stoichiometric C:P and N:P ratios of cells grown under 2-AEP are in-between the P-depleted and DIP-replete groups. This study provided evidence that biogenic phosphonates can be adopted as alternative phosphorus sources to support diatom growth and might have a profound effect on the elemental stoichiometry in the oligotrophic ocean.

Scientific significance statement

Phosphorus (P) is a major limiting macronutrient for primary productivity in the ocean, whilst the biologically mediated cycling of different P forms is less understood compared to carbon and nitrogen. Accounting for 25% of the marine dissolved organic phosphorus pool, phosphonate bioavailability by eukaryotic phytoplankton still remains discrepancies. In line with our hypothesis, here we report that a cosmopolitan diatomThalassiosira pseudonanacan utilize biogenic phosphonates 2-aminoethylphosphonic acid and 2-amino-3-phosphonopropionic acid to support cell growth, with deviated cellular C:N:P in comparison to that of P-replete cells. Furthermore, cells grown under lower temperature exhibit physiological adaptation (K-selection strategy) with the benefit of 2-AEP supplied in the medium. We provide the evidence that utilization of biogenic phosphonate is ubiquitous in diatom and it might have profound effect on elemental stoichiometry ratios in the environment. Filling in this missing puzzle piece provides us with a fresh perspective to elucidate the role of phosphonates in marine phosphorus cycle and biological pump.