bluuebunny/crossref_metadata_2025 huggingface dataset:
Creation and Expansion of a Mixed Patient Intermediate Care Unit to Improve ICU Capacity
Authors: Kistler Emmett A. , Klatt Elaine , Raffa Jesse D. , West Phyllis , Fitzgerald Jacqueline A. , Barsamian Jennifer , Rollins Scott , Clements Charlotte M. , Hickox Murray Shelby , Cocchi Michael N. , Yang Julius , Hayes Margaret M.
Published: October 2023

OBJECTIVES:

ICU capacity strain is associated with worsened outcomes. Intermediate care units (IMCs) comprise one potential option to offload ICUs while providing appropriate care for intermediate acuity patients, but their impact on ICU capacity has not been thoroughly characterized. The aims of this study are to describe the creation of a medical-surgical IMC and assess how the IMC affected ICU capacity.

DESIGN:

Descriptive report with retrospective cohort review.

SETTING:

Six hundred seventy-three-bed tertiary care academic medical center with 77 ICU beds.

PATIENTS:

Adult inpatients who were admitted to the IMC.

INTERVENTIONS:

An interdisciplinary working group created an IMC which was located on a general ward. The IMC was staffed by hospitalists and surgeons and supported by critical care consultants. The initial maximum census was three, but this number increased to six in response to heightened critical care demand. IMC admission criteria also expanded to include advanced noninvasive respiratory support defined as patients requiring high-flow nasal cannula, noninvasive positive pressure ventilation, or mechanical ventilation in patients with tracheostomies.

MEASUREMENTS AND MAIN RESULTS:

The primary outcome entailed the number of ICU bed-days saved. Adverse outcomes, including ICU transfer, intubation, and death, were also recorded. From August 2021 to July 2022, 230 patients were admitted to the IMC. The most frequent IMC indications were respiratory support for medical patients and post-operative care for surgical patients. A total of 1023 ICU bed-days were made available. Most patients were discharged from the IMC to a general ward, while 8% of all patients required transfer to an ICU within 48 hours of admission. Intubation (2%) and death (1%) occurred infrequently within 48 hours of admission. Respiratory support was the indication associated with the most ICU transfers.

CONCLUSIONS:

Despite a modest daily census, an IMC generated substantial ICU bed capacity during a time of peak critical care demand.
Comparative oral metagenome insight into acute and chronic root canal infections
Authors: Kumari K. Swapna , Dixit Sangita , Gaur Mahendra , Behera Dibyajyoti Uttameswar , Das Patitapabana , Subudhi Enketeswara , Rath Shakti
Published: October 2023

Background:

In the dynamic progression of root canal infections, the resultant change in environmental conditions directs the adaptation of the microbiome in terms of richness, evenness, and diversity.

Objective:

The goal of this study is to contrast the interradicular bacterial community structures of teeth in acute and chronic stages and investigate potential microorganisms associated with persistent apical periapical infections.

Methods:

Interradicular samples were collected from 10 teeth in the apical periodontitis group and 10 teeth in the chronic apical periodontitis group. High-throughput next-generation sequencing (NGS)–based microbial identification through the Illumina platform was used to characterize the complex intraradicular microbial communities in acute and chronic root canal infections. Results: Bacteria were the major domain, with a prevalence of > 97% (acute cases: 98.11 % and chronic cases: 97.6%) compared to eukaryotes and archaea. Bacterial diversity was relatively higher in acute compared to chronic conditions under 10 and 9 phyla, 79 and 64 genera, and 172 and 135 species, respectively. These endodontically infecting bacteria belonged to
Firmicutes
(47.21 %),
Bacteroidetes
(20.07%), and
Proteobacteria
(10.72%) in acute conditions, while in the chronic stage,
Firmicutes
(40.85%),
Proteobacteria
(27.80%), and
Actinobacteria
(14.79%) were abundant. The phylum
Candidatus Saccharibacteria
was exclusively found in acute samples
. Spirochaetes
and
Synergistetes
were found predominantly in acute infections compared to chronic infections.
Bacillus
and
Lactobacillus
were found in equal and highest abundance under the phylum
Firmicutes
in both conditions. Conclusion: This study provides information on the differential microbial community present in the apical root canal system of teeth with acute and chronic apical periodontitis and contributes to new approaches or channels for future research on preventive measures and therapeutic protocols during disease progression and treatment. However, functional characterization and detection of antimicrobial resistance in these two clinical conditions can supplement these findings for deciding routine drug treatment for periodontal infections.
Chicken bone-induced ileal perforation peritonitis mimicking duodenal perforation peritonitis: a case report
Authors: Dev Santosh , Pokhrel Kailash Mani , Mulmi Utsha , Devkota Shishir , Dev Barsha , Bhattarai Abhishek
Published: October 2023

Introduction:

Foreign body ingestion can lead to bowel perforation and peritonitis. We present a case of a 54-year-old male who ingested a chicken bone, resulting in ileal perforation that mimicked duodenal perforation peritonitis.

Case Presentation:

The patient has a history of peptic ulcer disease and regularly used non-steroidal anti-inflammatory drugs over the counter, adding more evidence to the provisional diagnosis of duodenal perforation. Exploratory laparotomy revealed the ileal perforation and the chicken bone was successfully removed. Wedge resection of the perforated segment and ileo-ileal anastomosis were performed.

Discussion:

Although history, examination, and investigation were more in favor of duodenal ulcer, our patient had ileal perforation due to chicken bone. Prompt identification and early surgical intervention are crucial to prevent complications and reduce mortality rates. The patient had an uneventful recovery.

Conclusion:

Timely referral to a tertiary care center is essential for early surgical intervention and successful management of bowel perforation caused by a foreign body.
Pituitary macroadenoma with panhypopituitarism masquerading as schizophrenia: a diagnostic dilemma managed conservatively
Authors: Ghimire Sagun , Simkhada Suman , Sah Saroj , Subedi Amit
Published: October 2023

Introduction and importance:

Secretory pituitary macroadenoma also known as prolactinoma are benign neoplasm comprising very minimal cases of intracranial masses. Among the various presentation suggestive of panhypopituitarism, psychosis, and features of schizophrenia is very rarely seen. In the majority of cases, neurosurgical intervention for the excision of tumor is considered a standard treatment modality but conservative management with dopamine agonist and steroids have also been shown to provide an optimal level of care also improving the quality of level of patient.

Case presentation:

A 42-year-old Asian male presented with a history of talking to self, delusion of persecution, over talkativeness, hallucination, increased suspiciousness, and history of lost and found in the streets where he was working as a migrant worker. The patient was initially managed in line of schizophrenia with the antipsychotics drug of choice. On further assessment there was no improvement of psychiatric symptoms but they further deteriorated with additional neuropsychiatric symptoms; hence, MRI brain was carried out. Following which, the diagnosis of pituitary macroadenoma was confirmed and further more hormonal analysis was done, which showed findings suggestive of panhypopituitarism. The patient was then managed conservatively with dopamine agonist and steroids, which showed rapid improvement of psychiatric symptoms with a massive reduction in the size of the pituitary macroadenoma.

Clinical discussion:

With the incidence of 100 per million cases pituitary adenomas are considered locally invading with the characteristic compression of the surrounding structure, presenting as visual hallucinations, olfactory hallucinations, episodes of losing time, apathy, and features suggestive of adrenal insufficiency, hypogonadotrophic hypogonadism, and symptoms secondary to hormonal imbalance such as hypothyroidism. Psychiatric symptomatic presentations are considered a very rare presentation in cases of pituitary macroadenoma. Also, psychiatric features and symptoms of psychosis are associated with prolcatinomas through idiopathic mechanism and the basic casualty has not been established. Surgical intervention such as trans-sphenoidal resection of the mass can be undertaken in case where mass effects is present but long-term remission and prognosis is found not to be fruitful. Conservative treatment with dopamine agonist such as cabergoline and steroids also plays a meaningful role in abrupt management in such cases.

Conclusion:

Pituitary macroadenoma presenting as a patient of schizophrenia is noted very rarely in medical literature; hence, investigations in view of neurosurgical diagnosis in cases presenting as psychosis should be considered for ideal holistic management. Conservative management can also be a breakthrough treatment modality in complete recovery of pituitary macroadenoma.
A Tiny Historical Slice of Case Management
Authors: Powell Suzanne K.
Published: October 2023

National Case Management Week in 2023 is October 8–14. This celebration of case managers has been going on since 1999 after the Individual Case Management Association (ICMA) and the Case Management Society of America (CMSA) merged. Since the 1990s, case management has evolved significantly; this evolution impacts every case manager, on every case by case, year by year.
The Determinants of Elevated Pathobiological Determination of Atherosclerosis in Youth Risk Score in Perinatally HIV-Infected Adolescents in South Africa
Authors: Mahtab Sana , Frigati Lisa J. , Ntusi Ntobeko A. B. , Nyathi Mothabisi , Asafu-Agyei Nana Akua , Myer Landon , Zar Heather J. , Jao Jennifer
Published: October 2023

Background:

Youth living with perinatally acquired HIV infection (YLPHIV) are at risk of developing atherosclerotic cardiovascular disease.

Methods:

We determined the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary arteries (CA) and abdominal aorta (AA) risk scores among YLPHIV who are ≥15 years old in Cape Town Adolescent and Antiretroviral Cohort. PDAY score was calculated using non–high-density lipoprotein, high-density lipoprotein cholesterol, hyperglycemia, hypertension, obesity, and smoking; a score ≥1 was considered elevated. HIV viremia was categorized as sustained (SV) = viral load (VL) >50 copies/mL, transient (TV) = mix of VL >50 and ≤50 copies/mL, or sustained-virologic suppression = VL <50 copies/mL throughout the study. Among YLPHIV, logistic models were fit to assess factors associated with elevated PDAY.

Results:

Overall, 218 YLPHIV [median age 16.8 (interquartile range: 15.9–17.8) years, male 47%] were included. Among YLPHIV, 8% (n = 17) had SV, and 54% (n = 118) had TV. Median antiretroviral therapy (ART) duration was 12 (interquartile range: 8–14) years. Among YLPHIV, 30.3% and 18.4% had elevated PDAY for CA and AA, respectively.

Among YLPHIV, SV [adjusted odds ratio (aOR) = 18.4, P < 0.01] and TV (aOR = 2.10, P = 0.04) compared with virologic suppression and ART duration in years (aOR = 1.12, P = 0.03) were associated with elevated CA. Male sex was associated with both elevated CA and AA (aOR = 2.14, P = 0.02, and aOR = 3.43, P = 0.01, respectively) and association of SV with elevated AA (aOR = 3.24, P = 0.09).

Conclusions:

A substantial proportion of YLPHIV have PDAY scores reflecting increased aggregate atherosclerotic risk. Among YLPHIV, viremia, lifetime ART duration, and male sex contribute to this risk, highlighting the importance of HIV control and the need to monitor cardiometabolic health.
Risk Factors for Postoperative Infections Following Appendectomy of Complicated Appendicitis: A Meta-analysis and Retrospective Single-institutional Study
Authors: Cironi Katherine , Albuck Aaron L. , McLafferty Bryant , Mortemore Alison K. , McCarthy Christina , Hussein Mohammad , Issa Peter P. , Metz Tyler , Herrera Marcela , Toraih Eman , Taghavi Sharven , Kandil Emad , Turner Jacquelyn
Published: October 2023

Patients with complicated appendicitis have an increased risk for postoperative infections. Potential risk factors for postoperative infections through a meta-analysis and retrospective chart review are discussed. A meta-analysis consisting of 35 studies analyzing complicated appendicitis treated with an appendectomy noting at least 1 postoperative infection was performed. A retrospective review was then conducted in patients diagnosed with complicated appendicitis after appendectomy. Of 5326 patients in total, 15.4% developed postoperative infections. Laparoscopic surgery and perioperative hyperoxygenation were found to be protective factors for the development of infection. Retrospectively, 53.2% of patients presented with complicated appendicitis. Patients with complicated appendicitis were more likely to be older in age and have an increased length of stay. Patient demographics, operative time, and comorbid status had no effect on postoperative infection or readmission rate. Physicians should strongly consider minimally invasive techniques to treat all cases of complicated appendicitis irrespective of comorbidities, age, sex, or body mass index.
Chromatin gatekeeper and modifier CHD proteins in development, and in autism and other neurological disorders
Authors: Muhammad Tahir , Pastore Stephen F. , Good Katrina , Ausió Juan , Vincent John B.
Published: October 2023

Chromatin, a protein–DNA complex, is a dynamic structure that stores genetic information within the nucleus and responds to molecular/cellular changes in its structure, providing conditional access to the genetic machinery. ATP-dependent chromatin modifiers regulate access of transcription factors and RNA polymerases to DNA by either “opening” or “closing” the structure of chromatin, and its aberrant regulation leads to a variety of neurodevelopmental disorders. The chromodomain helicase DNA-binding (CHD) proteins are ATP-dependent chromatin modifiers involved in the organization of chromatin structure, act as gatekeepers of genomic access, and deposit histone variants required for gene regulation. In this review, we first discuss the structural and functional domains of the CHD proteins, and their binding sites, and phosphorylation, acetylation, and methylation sites. The conservation of important amino acids in SWItch/sucrose non-fermenting (SWI/SNF) domains, and their protein and mRNA tissue expression profiles are discussed. Next, we convey the important binding partners of CHD proteins, their protein complexes and activities, and their involvements in epigenetic regulation. We also show the ChIP-seq binding dynamics for CHD1, CHD2, CHD4, and CHD7 proteins at promoter regions of histone genes, as well as several genes that are critical for neurodevelopment. The role of CHD proteins in development is also discussed. Finally, this review provides information about CHD protein mutations reported in autism and neurodevelopmental disorders, and their pathogenicity. Overall, this review provides information on the progress of research into CHD proteins, their structural and functional domains, epigenetics, and their role in stem cell, development, and neurological disorders.
The relationship between the number of COVID-19 vaccines and infection with Omicron ACE2 inhibition at 18-months post initial vaccination in an adult cohort of Canadian paramedics
Authors: Yap Justin , Kayda Iryna , Asamoah-Boaheng Michael , Haig Scott , Kirkham Tracy , Cheskes Sheldon , Demers Paul , Goldfarb David , Grunau Brian
Published: October 2023

The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has rapidly evolved since late 2019, due to highly transmissible Omicron variants. While most Canadian paramedics have received COVID-19 vaccination, the optimal ongoing vaccination strategy is unclear. We investigated neutralizing antibody (NtAb) response against wild-type (WT) Wuhan Hu-1 and Omicron BA.4/5 lineages based on the number of doses and past SARS-CoV-2 infection, at 18 months post initial vaccination (with a Wuhan Hu-1 platform mRNA vaccine [BNT162b2 or mRNA-1273}). Demographic information, previous COVID-19 vaccination, infection history, and blood samples were collected from paramedics 18 months post initial mRNA COVID-19 vaccine dose. Outcome measures were ACE2 percent inhibition against Omicron BA.4/5 and WT antigens. We compared outcomes based on number of vaccine doses (two vs. three) and previous SARS-CoV-2 infection status, using the Mann-Whitney U test. Of 657 participants, the median age was 40 years (IQR 33-50) and 251 (42%) were females. Overall, median percent inhibition to BA.4/5 and WT was 71.61% (IQR 39.44-92.82) and 98.60% (IQR 83.07-99.73), respectively. Those with a past SARS-CoV-2 infection had a higher median percent inhibition to BA.4/5 and WT, when compared to uninfected individuals overall and when stratified by two or three vaccine doses. When comparing two vs. three WT vaccine doses among SARS-CoV-2 negative participants, we did not detect a difference in BA.4/5 percent inhibition, but there was a difference in WT percent inhibition. Among those with previous SARS-CoV-2 infection(s), when comparing two vs. three WT vaccine doses, there was no observed difference between groups. These findings demonstrate that additional Wuhan Hu-1 platform mRNA vaccines did not improve NtAb response to BA.4/5, but prior SARS-CoV-2 infection enhances NtAb response.
Microbial Infection among SARS-COV-2 Infected Patients in a COVID-19 dedicated tertiary care hospital of Bangladesh: a Cross Sectional Study
Authors: Islam A N M Shamsul , Khanam Fahmida , Farhana Nasreen , Choudhury Rafaat , Jahan Naznin Akter , Uddin Mohammad Jamal , Refat Md. Nazmul Hassan , Nasreen Fatima
Published: October 2023

Objectives: This study aimed to determine patterns of respiratory, blood-borne, and uropathogenic microbial pathogens among SARS-CoV-2 infected patients in a COVID-19 dedicated hospital in Bangladesh.

Design:  Cross-sectional study
Setting: In a COVID-19 dedicated tertiary care Hospital, Dhaka, Bangladesh conducted from March to June 2021
Participants:  Hospitalized COVID 19 infected patients irrespective of age and sex
Primary and secondary outcome measures: Primary outcome measures were proportion of co-infection in COVID-19 patients and characterization of microbes causing co-infection. Secondary outcome measures were to find out if there is any relation between co-infection and age, co-infection and sex, co-infection and comorbidity.
Interventions: not applicable
Results:
Out of 79 patients, 61% were male, mean age was 49.53 years. Co-infection was seen in 7.7% patients and out of which 5.1% of isolates were from urine sample, followed by 2.6% from blood.  Bacteria isolated from urine were Enterococci (2.6%), coagulase negative Staphylococcus CONS (1.3%), and Enterobacter spp. (1.3%). Pseudomonas spp. was found in blood sample. Mixed growth was found in NS and TS with predominant species being Staphylococcus aureus, Streptococcus spp. At the time the data was collected, 55.7% of patients had been given antimicrobials, and 30.4% of patients had been given a single antimicrobial. HBsAg was positive in 1.3% patients. None were anti HCV or Dengue NS1Ag positive.
Conclusion: Microbial infection has been seen to be associated with SARS-CoV-2 infections and is of great value in prescribing antimicrobial and reducing fatal outcomes of hospitalized patients.
Continuing genomic evolution of the Neisseria meningitidis cc11.2 urethritis clade, NmUC: a narrative review
Authors: Rodriguez Emilio I. , Tzeng Yih-Ling , Stephens David S.
Published: October 2023

Neisseria meningitidis (Nm) is a bacterial pathogen responsible for invasive meningococcal disease. Though typically colonizing the nasopharynx, multiple outbreaks of meningococcal urethritis were first reported in 2015–2016; outbreaks originally presumed to be caused by

Neisseria gonorrhoeae

(Ng). Genomic analysis revealed that the Nm isolates causing these outbreaks were a distinct clade, and had integrated gonococcal DNA at multiple genomic sites, including the gonococcal denitrification apparatus aniA–norB, a partial gonococcal operon of five genes containing ispD, and the acetylglutamate kinase gene argB with the adjacent gonococcal locus NGO0843. The urethritis isolates had also deleted the group C capsule biosynthesis genes cssA/B/C and csc, resulting in loss of capsule. Collectively, these isolates form the

N. meningitidis

urethritis clade (NmUC). Genomic analysis of recent (2016–2022) NmUC isolates revealed that the genomic features have been maintained in the clade, implying that they are important for NmUC’s status as a urogenital pathogen. Furthermore, the analysis revealed the emergence of a sub-clade, designated NmUC-B, phylogenetically separated from the earlier NmUC-A. This sub-clade has integrated additional gonococcal alleles into the genome, including alleles associated with antimicrobial resistance. NmUC continues to adapt to a urethral niche and evolve as a urogenital pathogen.
NetTCR 2.2 - Improved TCR specificity predictions by combining pan- and peptide-specific training strategies, loss-scaling and integration of sequence similarity
Authors: Jensen Mathias Fynbo , Nielsen Morten
Published: October 2023

The ability to predict binding between peptides presented by the Major Histocompatibility Complex (MHC) class I molecules and T-cell receptors (TCR) is of great interest in areas of vaccine development, cancer treatment and treatment of autoimmune diseases. However, the scarcity of paired-chain data, combined with the bias towards a few well-studied epitopes, has challenged the development of pan-specific machine-learning (ML) models with accurate predictive power towards peptides characterized by little or no TCR data. To deal with this, we here benefit from a larger paired-chain peptide-TCR dataset and explore different ML model architectures and training strategies to better deal with imbalanced data. We show that while simple changes to the architecture and training strategies results in greatly improved performance, particularly for peptides with little available data, predictions on unseen peptides remain challenging, especially for peptides distant to the training peptides. We also demonstrate that ML models can be used to detect potential outliers, and that the removal of such outliers from training further improves the overall performance. Furthermore, we show that a model combining the properties of pan-specific and peptide-specific models achieves improved performance, and that performance can be further improved by integrating similarity-based predictions, especially when a low false positive rate is desirable. Moreover, in the context of the IMMREP 2022 benchmark, this updated modeling framework archived state-of-the-art performance. Finally, we show that combining all these approaches results in acceptable predictive accuracy for peptides characterized with as little as 15 positive TCRs. This observation thus places great promise on rapidly expanding the peptide covering of the current models for predicting TCR specificity. The final NetTCR 2.2 models are available athttps://github.com/mnielLab/NetTCR-2.2, and as a web server athttps://services.healthtech.dtu.dk/services/NetTCR-2.2/.
The NFκBDifis required for behavioral and molecular correlates of sleep homeostasis inDrosophila
Authors: O’Hara Michael K. , Saul Christopher , Handa Arun , Sehgal Amita , Williams Julie A.
Published: October 2023

The nuclear factor binding the κ light chain in B-cells (NFκB) is involved in a wide range of cellular processes including development, growth, innate immunity, and sleep. However, efforts have been limited toward understanding how specific NFκB transcription factors function in sleep.Drosophilafruit flies carry three genes encoding NFκB transcription factors,Dorsal,Dorsal Immunity Factor(Dif), andRelish. We previously found that loss of theRelishgene from fat body suppressed daily nighttime sleep, and abolished infection-induced sleep. Here we show thatDifregulates daily sleep and recovery sleep following prolonged wakefulness. Mutants ofDifshowed reduced daily sleep and suppressed recovery in response to sleep deprivation. Pan-neuronal knockdown ofDifstrongly suppressed daily sleep, indicating that in contrast toRelish,Diffunctions from the central nervous system to regulate sleep.

Based on the distribution of aDif-associated GAL4 driver, we hypothesized that its effects on sleep were mediated by the pars intercerebralis (PI). While RNAi knock-down ofDifin the PI reduced daily sleep, it had no effect on the recovery response to sleep deprivation. However, recovery sleep was suppressed when RNAi knock-down ofDifwas distributed across a wider range of neurons. Induction of thenemuri(nur) antimicrobial peptide by sleep deprivation was suppressed inDifmutants and pan-neuronal over-expression ofnuralso suppressed theDifmutant phenotype. Together, these findings indicate thatDiffunctions from brain to targetnemuriand to promote sleep.

Statement of Significance

NFκB transcription factors drive inflammatory processes that underly a multitude of human diseases that are accompanied by sleep disturbance. However, genetic studies in mammals that investigate a function of NFκB in sleep have been limited. Using genetic approaches in theDrosophilafruit fly, we show that theDifNFκB, homologous to theRelfamily of NFκBs in humans, functions from neuronal tissue to regulate daily sleep and to mediate responses to sleep loss. These findings enhance our understanding of the role of a specific NFκB gene in sleep regulation.
Animal Emotions and Consciousness: Researchers’ Perceptions, Biases, and Prospects for Future Progress
Authors: Zipple Matthew N , Hazelwood Caleb , Webster Mackenzie F , Benítez Marcela E
Published: October 2023

Do animals have emotions? Scientists and philosophers have long struggled with this question, with debates ranging from whether animals experience an “internal world” to whether we are capable of studying it. Recently, theoretical, and methodological advances have rekindled this debate, yet, it is unclear where the scientific consensus on these topics lies today. To address this gap, we administered a survey of professional animal behavior researchers to assess perceptions regarding (1) the taxonomic distribution of emotions and consciousness in non-human animals, (2) respondents’ confidence in this assessment, and (3) attitudes towards potential for progress and possible pitfalls when addressing these questions. In general, animal behavior researchers (n=100) ascribed emotionality and consciousness to a broad swath of the animal taxa, including non-human primates, other mammals, birds, and cephalopods, with varying degrees of confidence. There was a strong positive relationship between how likely a respondent was to attribute emotions to a given taxa and their confidence in that assessment, with respondents assuming an absence of emotions and consciousness when they were unsure. In addition, respondents’ assessments were shaped by several traits (e.g., advanced cognitive abilities, consciousness) that they also admitted were not necessary for an animal to experience emotions. Ultimately, a large majority of researchers were optimistic that tools either currently exist or will exist in the future to rigorously address these questions (>85%) and that animal behavior, as a field, should do more to encourage emotions research (71%). We discuss implications of our findings for publication bias, ethical considerations, and identify an emergent consensus for the need of a functional definition of emotions to facilitate future work.

Significance Statement

Emotions and consciousness are fundamental components of human experience—these phenomena are central to our behavior, relationships, and sense of meaning. Whether these experiences are shared by non-human animals has long been a subject of philosophical and scientific debate. In this paper we describe, for the first time, results from a survey of animal behavior researchers regarding their perceptions of these questions and the ability of science to answer them. Researchers ascribe emotions and consciousness to many taxa, and their likelihood of doing was strongly predicted by phylogeny and researchers’ confidence in their answers. We hope these results spur additional interdisciplinary collaboration to rigorously pursue these questions and create a baseline for future comparisons to track scientific attitudes over time.

“I have chosen bats instead of wasps or flounders because if one travels too far down the phylogenetic tree, people gradually shed their faith that there is experience there at all”--Thomas Nagel
The Interferon-inducible NAMPT acts as a protein phosphoribosylase to restrict viral infection
Authors: Zhang Shu , Xie Na , Liu Yongzhen , Qin Chao , Savas Ali Can , Wang Ting-Yu , Li Shutong , Rao Youliang , Shambayate Alexandra , Chou Tsui-Fen , Brenner Charles , Huang Canhua , Feng Pinghui
Published: October 2023

As obligate intracellular pathogens, viruses often activate host metabolic enzymes to supply intermediates that support progeny production. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the salvage NAD+synthesis, is an interferon-inducible protein that inhibits the replication of several RNA and DNA viruses with unknown mechanism. Here we report that NAMPT restricts herpes simplex virus 1 (HSV-1) replication via phosphoribosyl-hydrolase activity toward key viral structural proteins, independent of NAD+synthesis. Deep mining of enriched phosphopeptides of HSV-1-infected cells identified phosphoribosylated viral structural proteins, particularly glycoproteins and tegument proteins. Indeed, NAMPT de-phosphoribosylates viral proteinsin vitroand in cells. Chimeric and recombinant HSV-1 carrying phosphoribosylation-resistant mutations show that phosphoribosylation promotes the incorporation of structural proteins into HSV-1 virions and subsequent virus entry. Moreover, loss of NAMPT renders mice highly susceptible to HSV-1 infection. The work describes a hidden enzyme activity of a metabolic enzyme in viral infection and host defense, offering a system to interrogate roles of phosphoribosylation in metazoans.
Using data-dependent and independent hybrid acquisitions for fast liquid chromatography-based untargeted lipidomics
Authors: Tokiyoshi Kanako , Matsuzawa Yuki , Takahashi Mikiko , Takeda Hiroaki , Hasegawa Mayu , Miyamoto Junki , Tsugawa Hiroshi
Published: October 2023

Untargeted lipidomics using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) has become an essential technique for large cohort studies. When a fast LC gradient of less than 10 min is used for the rapid screening of lipids, the annotation rate decreases because of the lower coverage of the MS/MS spectra caused by the narrow peak width. We propose a systematic procedure to achieve a high annotation rate in fast LC-based untargeted lipidomics by integrating data-dependent acquisition (DDA), and sequential window acquisition of all theoretical mass spectra data-independent acquisition (SWATH-DIA) techniques with the updated MS-DIAL program. Our strategy uses variable SWATH-DIA methods for quality control (QC) samples, which are a mixture of biological samples analyzed multiple times to correct MS signal drifts. In contrast, biological samples are analyzed using DDA to facilitate the structural elucidation of lipids using the pure spectrum to the maximum extent. We demonstrate our workflow using an 8.6 min LC gradient, where QCs are analyzed using five different SWATH-DIA methods. The results indicated that using both DDA and SWATH-DIA achieves 2.0-fold annotation coverage from publicly available benchmark data obtained by a fast LC-DDA-MS technique and offers 94.5% lipid coverage compared with the benchmark dataset from a 25 min LC gradient. Our study demonstrated that harmonized improvements in the analytical conditions and informatics tools provide a comprehensive lipidome in fast LC-based untargeted lipidomics, not only for large-scale studies but also for small-scale experiments, contributing to both clinical applications and basic biology.
The Distal-Proximal Relationships Among the Human Moonlighting Proteins: Evolutionary hotspots and Darwinian checkpoints
Authors: Nawn Debaleena , Hassan Sk. Sarif , Sil Moumita , Ghosh Ankita , Goswami Arunava , Basu Pallab , Dayhoff Guy W. , Lundstrom Kenneth , Uversky Vladimir N.
Published: October 2023

Moonlighting proteins, known for their ability to perform multiple, often unrelated functions within a single polypeptide chain, challenge the traditional “one gene, one protein, one function” paradigm. As organisms evolved, their genomes remained relatively stable in size, but the introduction of post-translational modifications and sub-strategies like protein promiscuity and intrinsic disorder enabled multifunctionality. Enzymes, in particular, exemplify this phenomenon, engaging in unrelated processes alongside their primary catalytic roles. This study employs a systematic, quantitative informatics approach to shed light on human moonlighting protein sequences. Phylogenetic analyses of human moonlighting proteins are presented, elucidating the distal-proximal relationships among these proteins based on sequence-derived quantitative features. The findings unveil the captivating world of human moonlighting proteins, urging further investigations in the emerging field of moonlighting proteomics, with the potential for significant contributions to our understanding of multifunctional proteins and their roles in diverse cellular processes and diseases.
E. coliRecBCD Nuclease Domain Regulates Helicase Activity but not Single Stranded DNA Translocase Activity
Authors: Fazio Nicole , Mersch Kacey N. , Hao Linxuan , Lohman Timothy M.
Published: October 2023

Much is still unknown about the mechanisms by which helicases unwind duplex DNA. Whereas structure-based models describe DNA unwinding as a consequence of mechanically pulling the DNA duplex across a wedge domain in the helicase by the single stranded (ss)DNA translocase activity of the ATPase motors, biochemical data indicate that processive DNA unwinding by theE. coliRecBCD helicase can occur in the absence of ssDNA translocation of the canonical RecB and RecD motors. Here, we present evidence that dsDNA unwinding is not a simple consequence of ssDNA translocation by the RecBCD motors. Using stopped-flow fluorescence approaches, we show that a RecB nuclease domain deletion variant (RecBΔNucCD) unwinds dsDNA at significantly slower rates than RecBCD, while the rate of ssDNA translocation is unaffected. This effect is primarily due to the absence of the nuclease domain and not the absence of the nuclease activity, since a nuclease-dead mutant (RecBD1080ACD), which retains the nuclease domain, showed no significant change in rates of ssDNA translocation or dsDNA unwinding relative to RecBCD on short DNA substrates (≤ 60 base pairs). This indicates that ssDNA translocation is not rate-limiting for DNA unwinding. RecBΔNucCD also initiates unwinding much slower than RecBCD from a blunt-ended DNA, although it binds with higher affinity than RecBCD. RecBΔNucCD also unwinds DNA ∼two-fold slower than RecBCD on long DNA (∼20 kilo base pair) in single molecule optical tweezer experiments, although the rates for RecBD1080ACD unwinding are intermediate between RecBCD and RecBΔNucCD. Surprisingly, significant pauses occur even in the absence ofchi(crossover hotspot instigator) sites. We hypothesize that the nuclease domain influences the rate of DNA base pair melting, rather than DNA translocation, possibly allosterically. Since the rate of DNA unwinding by RecBCD also slows after it recognizes achisequence, RecBΔNucCD may mimic a post-chistate of RecBCD.
Active regulatory elements recruit cohesin to establish cell-specific chromatin domains
Authors: Georgiades Emily , Harrold Caroline L. , Roberts Nigel , Kassouf Mira , Riva Simone G. , Sanders Edward , Francis Helena S. , Blayney Joseph , Oudelaar A. Marieke , Milne Thomas A. , Higgs Douglas R. , Hughes Jim
Published: October 2023

As the structure of the genome is analysed at ever increasing resolution it is becoming clear that there is considerable variation in the 3D chromatin architecture across different cell types. It has been proposed that this may, in part, be due to increased recruitment of cohesin to activated cis-elements (enhancers and promoters) leading to cell-type specific loop extrusion underlying the formation of new subTADs. Here we show that cohesin correlates well with the presence of active enhancers and this varies in an allele-specific manner with the presence or absence of polymorphic enhancers which vary from one individual to another. Using the alpha globin cluster as a model, we show that when all enhancers are removed, peaks of cohesin disappear from these regions and the erythroid specific subTAD is no longer formed. Re-insertion of the major alpha globin enhancer (R2) is associated with the appearance of a new peak of cohesin at the site of insertion. In complementary experiments insertion of R2 into a “neutral” region of the genome recruits cohesin, induces transcription and creates a new large (75kb) erythroid specific domain. Together these findings support the proposal that active enhancers recruit cohesin, stimulate loop extrusion and promote the formation of cell specific subTADs.
On multiple infections by parasites with complex life cycles
Authors: Nguyen Phuong L. , Gokhale Chaitanya S.
Published: October 2023

Host manipulation is a common strategy of parasites with complex life cycles. It directly affects predator-prey dynamics in trophically transmitted parasites. Theoretical studies suggest that predation-enhancing manipulation of-ten decimates the prey population, making parasites prone to extinction. Host manipulation, however, can also reduce predation due to conflicting interests when multiple parasites infect a host, which is often neglected in theoretical studies. Misaligned interests of coinfecting parasites can occur due to limited carrying capacity or parasitoid developmental stage. Including this realistic complexity in a mathematical model, the results depart from previous studies substantially. We show that coinfecting multi-trophic parasites can preserve the predator-prey system and themselves through manipulation and reproduction parameters. Our study highlights the necessity of and provides the means for incorporating the reality of multiple parasites and their multi-trophic life cycles into the theory of parasite ecology.
BTR: A Bioinformatics Tool Recommendation System
Authors: Green Ryan , Qu Xufeng , Liu Jinze , Yu Tingting
Published: October 2023

Motivation

The rapid expansion of Bioinformatics research has resulted in a vast array of computational tools utilized in the development of scientific analysis pipelines. However, constructing these pipelines is a laborious and intricate task, one which demands extensive domain knowledge and careful consideration at all stages. As the Bioinformatics landscape continues to evolve, researchers, both novice and expert, may find themselves overwhelmed when working in unfamiliar fields. Consequently, this may result in the selection of unsuitable or suboptimal tools during workflow development.

Results

In this paper, we propose the Bioinformatics Tool Recommendation system (BTR), an innovative deep learning model designed to recommend the most suitable tools for a given workflow-in-progress. BTR utilizes recent advances in graph neural network technology and introduces a novel approach, representing the entire workflow as a graph to capture essential context and structural information. Additionally, natural language processing techniques are integrated to enhance the quality of tool recommendations by analyzing associated tool descriptions. Experiments demonstrate that BTR outperforms the existing Galaxy tool recommendation system, highlighting its potential to greatly facilitate scientific workflow construction.

Availability and implementation

The Python source code is available athttps://github.com/ryangreenj/bioinformatics_tool_recommendation
Network analyses reveal D clade ethylene response factors as major regulators of jasmonic acid-mediated resistance to early blight disease complex in tomato
Authors: Tominello-Ramirez Christopher , Muñoz Hoyos Lina , Oubounyt Mhaned , Stam Remco
Published: October 2023

Resistance mechanisms to early blight disease complex (EBDC) in tomato remain obscure given its polygenic and quantitative nature. We investigated the early defense responses of Heinz 1706 tomato to EBDC using RNA-seq. We observed distinct transcriptional reprofiling upon exposure to two EBDC isolates and the PAMP chitin. Avirulent isolate CS046 (Alternaria alternata) elicited a vigorous defense response in the host, whilst the virulent isolate 1117-1 (Alternariasect.Porri) showed subdued gene expression, suggesting a suppression of defense responses during compatible pathogenesis. We emphasize the specific roles ofETHYLENE RESPONSE FACTORs(ERFs) in defense against EBDC, with a particular focus on the D cladeERFs. Co-expression network analysis revealed the principal genes in early defense responses to EBDC are secondary metabolite biosynthesis genes, transcription factors, and hormone response genes. We constructed a gene regulatory network and predicted novel hub genes as putative global regulators of the defense response, including the D cladeERFs, WRKY, andNACtranscription factors. Our work highlights the failure of virulent EBDC pathogenesis to elicit hormone responses that suppress cell death. Additionally, we found a selective induction for specific ERFs that strongly influence the topology of the EBDC defense transcriptional network.
Development and preliminary testing of Health Equity Across the AI Lifecycle (HEAAL): A framework for healthcare delivery organizations to mitigate the risk of AI solutions worsening health inequities
Authors: Kim Jee Young , Hasan Alifia , Kellogg Kate , Ratliff William , Murray Sara , Suresh Harini , Valladares Alexandra , Shaw Keo , Tobey Danny , Vidal David , Lifson Mark , Patel Manesh , Raji Inioluwa Deborah , Gao Michael , Knechtle William , Tang Linda , Balu Suresh , Sendak Mark
Published: October 2023

The use of data driven technologies such as Artificial Intelligence (AI) and Machine Learning (ML) is growing in healthcare. However, the proliferation of healthcare AI tools has outpaced regulatory frameworks, accountability measures, and governance standards to ensure safe, effective, and equitable use. To address these gaps and tackle a common challenge faced by healthcare delivery organizations, a case based workshop was organized, and a framework was developed to evaluate the potential impact of implementing an AI solution on health equity. The Health Equity Across the AI Lifecycle (HEAAL) is designed with extensive engagement of clinical, operational, technical, and regulatory leaders across healthcare delivery organizations and ecosystem partners in the US. It assesses 5 equity assessment domains, including accountability, fairness, fitness for purpose, reliability and validity, and transparency, across the span of eight key decision points in the AI adoption lifecycle. It is a process oriented framework containing 37 step by step procedures for evaluating an existing AI solution and 34 procedures for evaluating a new AI solution in total. Within each procedure, it identifies relevant key stakeholders and data sources used to conduct the procedure. HEAAL guides how healthcare delivery organizations may mitigate the potential risk of AI solutions worsening health inequities. It also informs how much resources and support are required to assess the potential impact of AI solutions on health inequities.
The effects of the infarct volume on cytokines and immune status in patients with acute ischemic stroke
Authors: Su Xingqi , Zhao Lingmin , Ma Di , You Jiulin , Feng LiangShu , Wang Jing , Hao YuLei , Wang XinYu , Feng JiaChun
Published: October 2023

Objective

To investigate and analyze the effects of the infarct volume on cytokines and immune status in patients with acute ischemic stroke.

Methods

Patients with acute ischemic stroke that presented within 72 h of onset from October 2017 to October 2019 were enrolled. Patients with severe cerebral infarction (large-area cerebral infarction) (n=34) were enrolled and categorized as group A; Additionally, 33 patients with non-large-area cerebral infarction with matching baseline characteristics (sex and age) to group A were included in group B. We measured IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, and IFN-γ levels in serum using a cytometric bead array.In addition,we compared the absolute value of lymphocytes (LYM#), lymphocyte percentage (LYM%), neutrophil/lymphocyte ratio (NLR), cytokine levels, and immune status indicators (IFN-γ IL-4 ratio, TNF-α/IL-4 ratio, and TNF-α/IL-10 ratio) between groups A and B, and evaluated the effect of infarct size on inflammatory factors and immune status.

Results

Compared with group B, the LYM# and LYM% in group A were significantly lower, and the NLR and cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, and IFN-γ) levels were significantly higher. TNF-α/IL-4 ratio was significantly lower, and the IFN-γ/IL-4 ratio (P=0.09) and TNF-α/IL-10 ratio (P=0.146) in group A demonstrated a decreasing trend although not significant.

Conclusions

The immune status of patients with acute cerebral infarction is related to the infarct volume; patients with large-area cerebral infarction are more likely to develop immunosuppression.
A mechanistic study on the tolerance of PAM distal end mismatch by SpCas9
Authors: Dey Dhritiman , Chakravarti Rudra , Bhattacharjee Oindrila , Majumder Satyabrata , Chaudhuri Dwaipayan , Ahmed Kazi Tawsif , Bhattacharya Bireswar , Gautam Anupam , Singh Rajveer , Gupta Rahul , Ravichandiran Velayutham , Chattopadhyay Dhrubajyoti , Ghosh Abhrajyoti , Giri Kalyan , Roy Syamal , Ghosh Dipanjan
Published: October 2023

CRISPR-Cas9 is the newest technology available for targeted genome editing. It is very efficient and cheap compared to other genome editing techniques. However, its therapeutic application is limited due to its off-target activity. To have a better understanding of this off-target effect, we concentrated our efforts on its mismatch-prone PAM distal end. Current off-target prediction algorithms use RNA-DNA complementation derived energy as a major factor in predicting off-target effect. RNA-DNA complementation derived energy drives Cas9 conformational change, which in turn drives its functional activity. In the case of lower RNA-DNA complementarity, a partial conformational change occurs resulting in a slower reaction rate and partial activity. However, extensive mismatches are often tolerated despite lower complementation derived energy available from RNA: DNA duplex formation. Thus, the off-target activity of Cas9 depends directly on the nature of mismatches which in turn result in deviation of the active site of the enzyme due to structural instability in the duplex strand. In order to test the hypothesis, we have designed an array of mismatched target sites and performed in vitro and cell line-based experiments to assess the effects of PAM distal mismatches in Cas9 activity. For further mechanistic validation, Molecular dynamics simulation was performed and it revealed that certain mismatch mutations induced pronounced conformational instability within the RNA-DNA duplex, leading to elevated root mean square deviation (RMSD) values. We found that, target sites having mismatches in the 18th to 16th position upstream of the PAM showed no to little activity.