bluuebunny/crossref_metadata_2025_split huggingface dataset:
Explainable AI for Bioinformatics: Methods, Tools and Applications
Authors: Karim Md Rezaul , Islam Tanhim , Shajalal Md , Beyan Oya , Lange Christoph , Cochez Michael , Rebholz-Schuhmann Dietrich , Decker Stefan 
Published: July 2023

Abstract
Artificial intelligence (AI) systems utilizing deep neural networks and machine learning (ML) algorithms are widely used for solving critical problems in bioinformatics, biomedical informatics and precision medicine. However, complex ML models that are often perceived as opaque and black-box methods make it difficult to understand the reasoning behind their decisions. This lack of transparency can be a challenge for both end-users and decision-makers, as well as AI developers. In sensitive areas such as healthcare, explainability and accountability are not only desirable properties but also legally required for AI systems that can have a significant impact on human lives. Fairness is another growing concern, as algorithmic decisions should not show bias or discrimination towards certain groups or individuals based on sensitive attributes. Explainable AI (XAI) aims to overcome the opaqueness of black-box models and to provide transparency in how AI systems make decisions. Interpretable ML models can explain how they make predictions and identify factors that influence their outcomes. However, the majority of the state-of-the-art interpretable ML methods are domain-agnostic and have evolved from fields such as computer vision, automated reasoning or statistics, making direct application to bioinformatics problems challenging without customization and domain adaptation. In this paper, we discuss the importance of explainability and algorithmic transparency in the context of bioinformatics. We provide an overview of model-specific and model-agnostic interpretable ML methods and tools and outline their potential limitations. We discuss how existing interpretable ML methods can be customized and fit to bioinformatics research problems. Further, through case studies in bioimaging, cancer genomics and text mining, we demonstrate how XAI methods can improve transparency and decision fairness. Our review aims at providing valuable insights and serving as a starting point for researchers wanting to enhance explainability and decision transparency while solving bioinformatics problems. GitHub: https://github.com/rezacsedu/XAI-for-bioinformatics.
A machine learning based approach to identify carotid subclinical atherosclerosis endotypes
Authors: Chen Qiao Sen , Bergman Otto , Ziegler Louise , Baldassarre Damiano , Veglia Fabrizio , Tremoli Elena , Strawbridge Rona J , Gallo Antonio , Pirro Matteo , Smit Andries J , Kurl Sudhir , Savonen Kai , Lind Lars , Eriksson Per , Gigante Bruna 
Published: July 2023

Abstract

Aims
To define endotypes of carotid subclinical atherosclerosis.

Methods and results
We integrated demographic, clinical, and molecular data (n = 124) with ultrasonographic carotid measurements from study participants in the IMPROVE cohort (n = 3340). We applied a neural network algorithm and hierarchical clustering to identify carotid atherosclerosis endotypes. A measure of carotid subclinical atherosclerosis, the c-IMTmean-max, was used to extract atherosclerosis-related features and SHapley Additive exPlanations (SHAP) to reveal endotypes. The association of endotypes with carotid ultrasonographic measurements at baseline, after 30 months, and with the 3-year atherosclerotic cardiovascular disease (ASCVD) risk was estimated by linear (β, SE) and Cox [hazard ratio (HR), 95% confidence interval (CI)] regression models. Crude estimates were adjusted by common cardiovascular risk factors, and baseline ultrasonographic measures. Improvement in ASCVD risk prediction was evaluated by C-statistic and by net reclassification improvement with reference to SCORE2, c-IMTmean-max, and presence of carotid plaques. An ensemble stacking model was used to predict endotypes in an independent validation cohort, the PIVUS (n = 1061). We identified four endotypes able to differentiate carotid atherosclerosis risk profiles from mild (endotype 1) to severe (endotype 4). SHAP identified endotype-shared variables (age, biological sex, and systolic blood pressure) and endotype-specific biomarkers. In the IMPROVE, as compared to endotype 1, endotype 4 associated with the thickest c-IMT at baseline (β, SE) 0.36 (0.014), the highest number of plaques 1.65 (0.075), the fastest c-IMT progression 0.06 (0.013), and the highest ASCVD risk (HR, 95% CI) (1.95, 1.18–3.23). Baseline and progression measures of carotid subclinical atherosclerosis and ASCVD risk were associated with the predicted endotypes in the PIVUS. Endotypes consistently improved measures of ASCVD risk discrimination and reclassification in both study populations.

Conclusions
We report four replicable subclinical carotid atherosclerosis—endotypes associated with progression of atherosclerosis and ASCVD risk in two independent populations. Our approach based on endotypes can be applied for precision medicine in ASCVD prevention.
Nonsurgical hypoparathyroidism is associated with skeletal muscle dysfunction and restrictive lung disease
Authors: Babu Takasi Anush , Hashim Zia , Neyaz Zafar , Mani Vinita E , Jain Neeraj , Bhatia Eesh , Mishra Anjali , Sahoo Saroj Kumar 
Published: July 2023

Abstract

Context
Systematic assessment of skeletal muscle function is lacking in patients with nonsurgical hypoparathyroidism (HP). Whether muscle dysfunction involves respiratory muscles and results in restrictive lung disease (RLD) is not studied.

Objective
To assess skeletal muscle and pulmonary functions in patients with HP.

Design
Observational case–control study.

Methods
Thirty patients with HP (mean age 37.7 years, 60% males) and 40 age-, sex-, and body mass index (BMI)-matched healthy controls were assessed for skeletal muscle function by handgrip strength, the short physical performance battery (SPPB) test, dual-energy X-ray absorptiometry (DXA), and electromyography (EMG). Pulmonary function was assessed by spirometry, body plethysmography, diffusion lung capacity for carbon monoxide, and diaphragmatic ultrasound (DUS).

Results
Patients with HP had lower serum calcium (2.25 ± 0.15 vs 2.4 ± 0.12 mmol/L, P &lt; .001), serum magnesium (median [interquartile range] 0.74 [0.69-0.82] vs 0.78 [0.69-0.90] mmol/L, P = .04), handgrip strength (18.08 ± 8.36 vs 22.90 ± 7.77 kg, P = .01), and composite SPPB scores (9.5 [7-10] vs 12 [12-12], P &lt; .001) compared to healthy controls. Electromyographic evidence of myopathy was seen in 23% (5 of 22) of patients with HP but in none of the controls (P = .08). The prevalence of RLD was higher in the HP cohort compared to that in controls (24% vs 0%, P = .01). Diaphragmatic excursion (DE) (4.22 ± 1.38 vs 5.18 ± 1.53 cm, P = .01) and diaphragmatic thickness (DT) (3.79 ± 1.18 vs 4.28 ± 0.94 mm, P = .05) on deep inspiration were reduced in patients with HP.

Conclusion
Detailed testing of patients with HP without overt muscle and lung diseases revealed significant impairment in parameters of skeletal muscle function. Myopathy and RLD were observed in a considerable proportion of patients with HP.
A systematic review of how social connectedness influences associations between racism and discrimination on health outcomes
Authors: Ransome Yusuf , Valido Alberto D , Espelage Dorothy L , Clements Graceson L , Harrell Crystal , Eckel Caroline , Price Natalie , Nassau Rachel , Nyhan Kate , Taggart Tamara L 
Published: July 2023

Abstract
Racial discrimination is a well-known risk factor of racial disparities in health. Although progress has been made in identifying multiple levels through which racism and racial discrimination influences health, less is known about social factors that may buffer racism’s associations with health. We conducted a systematic review of the literature with a specific focus on social connectedness, racism, and health, retrieving studies conducted in the United States and published between January 1, 2012, and July 30, 2022, in peer-reviewed journals. Of the 787 articles screened, 32 were selected for full-text synthesis. Most studies (72%) were at the individual level, cross-sectional, and among community/neighborhood, school, or university samples. Studies had good methodological rigor and low risk of bias. Measures of racism and racial discrimination varied. Discrimination scales included unfair treatment because of race, schedule of racist events, experiences of lifetime discrimination, and everyday discrimination. Measures of social connectedness (or disconnectedness) varied. Social-connectedness constructs included social isolation, loneliness, and social support. Mental health was the most frequently examined outcome (75%). Effect modification was used in 56% of studies and mediation in 34% of studies. In 81% of studies, at least 1 aspect of social connectedness significantly buffered or mediated the associations between racism and health. Negative health associations were often weaker among people with higher social connectedness. Social connectedness is an important buffering mechanism to mitigate the associations between racial discrimination and health. In future studies, harmonizing metrics of social connectedness and racial discrimination can strengthen causal claims to inform interventions.
Sleep need, the key regulator of sleep homeostasis, is indicated and controlled by phosphorylation of threonine 221 in salt-inducible kinase 3
Authors: Li Yang , Li Chengang , Liu Yuxiang , Yu Jianjun , Yang Jingqun , Cui Yunfeng , Wang Tao V , Li Chaoyi , Jiang Lifen , Song Meilin , Rao Yi 
Published: July 2023

Abstract
Sleep need drives sleep and plays a key role in homeostatic regulation of sleep. So far sleep need can only be inferred by animal behaviors and indicated by electroencephalography (EEG). Here we report that phosphorylation of threonine (T) 221 of the salt-inducible kinase 3 (SIK3) increased the catalytic activity and stability of SIK3. T221 phosphorylation in the mouse brain indicates sleep need: more sleep resulting in less phosphorylation and less sleep more phosphorylation during daily sleep/wake cycle and after sleep deprivation (SD). Sleep need was reduced in SIK3 loss of function (LOF) mutants and by T221 mutation to alanine (T221A). Rebound after SD was also decreased in SIK3 LOF and T221A mutant mice. By contrast, SIK1 and SIK2 do not satisfy criteria to be both an indicator and a controller of sleep need. Our results reveal SIK3-T221 phosphorylation as a chemical modification which indicates and controls sleep need.
The questionable necessity of a new human right against being subject to automated decision-making
Authors: Abrusci Elena , Mackenzie-Gray Scott Richard 
Published: July 2023

Abstract
The development and interest in decision-making that is or can be automated have opened the doors of debate regarding the form and substance of related means of regulating its application. Part of this discourse involves proposals advocating for the creation of a new human right not to be subject to an automated decision. This article questions whether such a right is necessary in light of existing substantive rules under legal frameworks already applicable to automated decision-making, specifically data protection, non-discrimination and human rights. There are also procedural challenges requiring treatment if automated decision-making is to be adequately addressed by application of the law. Exploring these challenges helps appreciate the significance of ensuring that existing substantive law is better implemented for the purpose of protecting human beings in settings where automated decision-making poses risks to individuals and groups.
Short communication: evaluation of an endotoxin challenge and intraruminal bacterial inoculation model to induce liver abscesses in Holstein steers
Authors: McDaniel Zach S , Hales Kristin E , Nagaraja T G , Lawrence Ty E , Amachawadi Raghavendra G , Carroll Jeff A , Burdick Sanchez Nicole C , Galyean Michael L , Smock Taylor M , Ballou Michael A , Machado Vinicius S , Broadway Paul R 
Published: July 2023

AbstractHolstein steers (n = 40; initial body weight [BW] = 96.0 ± 10.5 kg) were individually housed in a climate-controlled barn to evaluate potential models for the genesis of liver abscesses (LA). In this 2 × 2 factorial, steers were balanced by BW and randomly assigned to one of two treatments: 1) intravenous saline injection followed by intraruminal bacterial inoculation with Fusobacterium necrophorum subsp. necrophorum (1 × 109 colony forming unit [CFU]/mL) and Salmonella enterica serovar Lubbock (1 × 106 CFU/mL; CON; n = 20 steers); or 2) intravenous injection with 0.25 µg/kg BW of lipopolysaccharide (LPS; Escherichia coli O111:B4) followed by intraruminal bacterial inoculation of F. necrophorum subsp. necrophorum (1 × 109 CFU/mL) and S. enterica serovar Lubbock (1 × 106 CFU/mL; LBI; n = 20 steers) and 1 of 2 harvest dates (3 or 10 d post LPS infusion). Body weights were recorded on days −4, −1, 3, and 10, and blood was collected for hematology on days −4, 3, and 10, relative to LPS infusion on day 0. Intraruminal bacterial inoculation occurred on day 1. Steers from each treatment group were harvested at two different time points on day 3 or 10 to perform gross pathological examination of the lung, rumen, liver, LA (if present), and colon. Feed disappearance was less for LBI than CON (P &lt; 0.01); however, BW did not differ (P = 0.33) between treatments. Neither treatment nor time differed for hematology (P ≥ 0.13), and no gross pathological differences were noted in the lung, liver, LA, or colon (P ≥ 0.25). A treatment × harvest date interaction was noted for ruminal pathology in which LBI had an increased percentage of abnormal rumen scores on day 3 (P &lt; 0.01). These results suggest that an LPS challenge in combination with intraruminal bacterial inoculation of pathogens commonly isolated from LA was not sufficient to induce LA in steers within 3 or 10 d (P = 0.95) when compared to CON. Further evaluation is needed to produce a viable model to investigate the genesis and prevention of LA in cattle.
Inhibition of Sirt2 Decreases ApoE Secretion in Astrocytes and Microglial Cells
Authors: Chen Yuxin , Zhou Chunyu , Abdelhamid Mona , Jung Cha-Gyun , Michikawa Makoto 
Published: July 2023

AbstractAmyloid-β (Aβ) accumulation caused by an imbalance of the production and clearance of Aβ in the brain is associated with the development of Alzheimer's disease (ad). Apolipoprotein E (ApoE) (the strongest genetic risk factor) enhances Aβ clearance, preventing Aβ deposition. Sirtuin 2 (Sirt2) is an NAD+-dependent histone deacetylase and its inhibition has been reported to ameliorate memory impairment in ad-like model mice. However, the role of Sirt2 in ApoE secretion is unknown. Here, we found that inhibition of Sirt2 activity in primary cultured astrocytes and BV2 cells decreased ApoE secretion, resulting in the accumulation of intracellular ApoE and inhibiting extracellular Aβ degradation. However, the reduction of Sirt2 protein level by Sirt2 siRNA decreased ApoE protein level, which ultimately reduces ApoE secretion. In addition, the knockdown of Sirt2 in the HEK293-APP cells also decreased levels of intracellular ApoE leading to reduction of its secretion, which is accompanied by increased Aβ levels without altering APP and APP processing enzymes. Our findings provide a novel role of Sirt2 in ApoE secretion.
A note on the worship of the Ācārya’s pādukās among the Śrīvaiṣṇavas
Authors: Anandakichenin Suganya 
Published: July 2023

Abstract
Worshipping the feet, footprints, and sandals (pādukā) of deities and revered people is a widespread practice across South Asia (and throughout the world) that cuts across belief systems. And the Śrīvaiṣṇavas are no exception: on the one hand, they receive the benediction of the Lord’s feet upon their heads in the form of the śaṭhāri, on a visit to a temple or a maṭha. And on the other hand, they worship the feet of their own Ācārya(s) and/or their pādukās, as well as those who belonged to their Ācārya lineage. In this article, I shall deal with the second practice, with a special focus on the manifold ways in which the Ācāryas’ pādukās are honoured institutionally in some of the Śrīvaiṣṇava maṭhas in South India, and on how the disciples of those religious institutions replicate some of the customs at home for their private worship. Given that there are many branches and families of Śrīvaiṣṇavas, differences in the worshipping practices have inevitably crept in, and in this article, I shall seek to understand those differences based on a few examples.
Nutritional approaches targeting mitochondria for the prevention of sarcopenia
Authors: Hahm Jeong-Hoon , Nirmala Farida S , Ha Tae Youl , Ahn Jiyun 
Published: July 2023

Abstract
A decline in function and loss of mass, a condition known as sarcopenia, is observed in the skeletal muscles with aging. Sarcopenia has a negative effect on the quality of life of elderly. Individuals with sarcopenia are at particular risk for adverse outcomes, such as reduced mobility, fall-related injuries, and type 2 diabetes mellitus. Although the pathogenesis of sarcopenia is multifaceted, mitochondrial dysfunction is regarded as a major contributor for muscle aging. Hence, the development of preventive and therapeutic strategies to improve mitochondrial function during aging is imperative for sarcopenia treatment. However, effective and specific drugs that can be used for the treatment are not yet approved. Instead studies on the relationship between food intake and muscle aging have suggested that nutritional intake or dietary control could be an alternative approach for the amelioration of muscle aging. This narrative review approaches various nutritional components and diets as a treatment for sarcopenia by modulating mitochondrial homeostasis and improving mitochondria. Age-related changes in mitochondrial function and the molecular mechanisms that help improve mitochondrial homeostasis are discussed, and the nutritional components and diet that modulate these molecular mechanisms are addressed.
Considerations for fitting occupancy models to data from eBird and similar volunteer-collected data
Authors: Hochachka Wesley M , Ruiz-Gutierrez Viviana , Johnston Alison 
Published: July 2023

Abstract
An occupancy model makes use of data that are structured as sets of repeated visits to each of many sites, in order to estimate the actual probability of occupancy (i.e. proportion of occupied sites) after correcting for imperfect detection using the information contained in the sets of repeated observations. We explore the conditions under which preexisting, volunteer-collected data from the citizen science project eBird can be used for fitting occupancy models. Because the majority of eBird’s data are not collected in the form of repeated observations at individual locations, we explore 2 ways in which the single-visit records could be used in occupancy models. First, we assess the potential for space-for-time substitution: aggregating single-visit records from different locations within a region into pseudo-repeat visits. On average, eBird’s observers did not make their observations at locations that were representative of the habitat in the surrounding area, which would lead to biased estimates of occupancy probabilities when using space-for-time substitution. Thus, the use of space-for-time substitution is not always appropriate. Second, we explored the utility of including data from single-visit records to supplement sets of repeated-visit data. In a simulation study we found that inclusion of single-visit records increased the precision of occupancy estimates, but only when detection probabilities are high. When detection probability was low, the addition of single-visit records exacerbated biases in estimates of occupancy probability. We conclude that subsets of data from eBird, and likely from similar projects, can be used for occupancy modeling either using space-for-time substitution or supplementing repeated-visit data with data from single-visit records. The appropriateness of either alternative will depend on the goals of a study and on the probabilities of detection and occupancy of the species of interest.
One health system’s morbidity and mortality conference survey: a step on the journey to organizational high reliability
Authors: Raper Steven E. , Sullivan Patricia G. , Levin Lawrence S. 
Published: July 2023

Background:
The goal of this study was to understand the state of morbidity and mortality conferences held throughout our health system. Assessment of current approaches is necessary for a journey toward organizational high reliability and an opportunity to reduce unnecessary variation in patient and process outcomes.

Study Design:
Forty-two anonymous surveys were distributed through the Health System’s Vice-chairs of Quality to those in the best position to answer questions. Answers from all departments and—where semi-autonomous—divisions were solicited. Categories, among others, included written guidelines, who presented, what events were chosen for presentation, and what was done with the data.

Results:
Forty-one surveys were returned. Seventeen departments or divisions have written guidelines as to which events should be reported. Twenty-two of the departmental or divisional conferences present selected cases, only 13 present all mortalities. Decisions on how events are classified are made most often by the director of Quality with 13 responses. There was no consensus on how best to enhance the clinical learning environment for residents and fellows.

Conclusion:
Opportunities identified by our survey to reduce practice variation include best practices for written guidelines and standardized classification formats for morbidity and mortality events. A mortality committee charged with event review and classification should be considered. Lastly, more effort should be made to enhance the clinical learning environment of trainees in event review and presentation.