bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening for obstructive sleep apnea in patients with cancer — a machine learning approach
Authors: Wong Karen A , Paul Ankita , Fuentes Paige , Lim Diane C , Das Anup , Tan Miranda
Published: November 2023

Background

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder associated with daytime sleepiness, fatigue, and increased all-cause mortality risk in patients with cancer. Existing screening tools for OSA do not account for the interaction of cancer-related features that may increase OSA risk.

Study Design and Methods

This is a retrospective study of patients with cancer at a single tertiary cancer institution who underwent a home sleep apnea test (HSAT) to evaluate for OSA. Unsupervised machine learning (ML) was used to reduce the dimensions and extract significant features associated with OSA. ML classifiers were applied to principal components and model hyperparameters were optimized using k-fold cross-validation. Training models for OSA were subsequently tested and compared with the STOP-Bang questionnaire on a prospective unseen test set of patients who underwent an HSAT.

Results

From a training dataset of 249 patients, kernel principal component analysis (PCA) extracted eight components through dimension reduction to explain the maximum variance with OSA at 98%. Predictors of OSA were smoking, asthma, chronic kidney disease, STOP-Bang score, race, diabetes, radiation to head/neck/thorax (RT-HNT), type of cancer, and cancer metastases. Of the ML models, PCA + RF had the highest sensitivity (96.8%), specificity (92.3%), negative predictive value (92%), F1 score (0.93), and ROC-AUC score (0.88). The PCA + RF screening algorithm also performed better than the STOP-Bang questionnaire alone when tested on a prospective unseen test set.

Conclusions

The PCA + RF ML model had the highest accuracy in screening for OSA in patients with cancer. History of RT-HNT, cancer metastases, and type of cancer were identified as cancer-related risk factors for OSA.
FabV, the Unique Enoyl-Acyl Carrier Protein Reductase in Xanthomonas arboricola pv. juglandis Associated with Walnut Bacterial Blight, Is Essential for the Growth and Confers Triclosan Resistance to the Strain
Authors: Li Feng , Deng Jiangli , Zhang Zhilin , Wang Cheng , Mao Yahui
Published: November 2023

Walnut bacterial blight caused by Xanthomonas arboricola pv. juglandis ( Xaj) is one of the most prevalent diseases of walnut ( Juglans spp.), causing significant reductions in nut yield and important losses in economy. Enoyl-acyl carrier protein (ACP) reductase (ENR) is one of the key enzymes involved in the biosynthesis of bacterial fatty acids. In this study, we identified a single ENR-encoding gene, RS10040, in the genome of the XajDW3F3 strain. Sequence alignment analysis suggested RS10040 as a candidate fabV gene in Xaj. Expression of XajfabV restored the growth of the Escherichia coli fabI temperature-sensitive mutant under a nonpermissive growth condition. In vitro assays demonstrated that XajFabV catalyzed enoyl-ACPs of various chain lengths to acyl-ACPs, demonstrating its role in de novo fatty acid biosynthesis. Furthermore, we confirmed that XajfabV is an essential gene for growth, as no XajfabV deletion mutant could be obtained, although XajfabV in the chromosome could be deleted after compensating with a functional ENR-encoding gene via an exogenous plasmid. The fabV replacement mutants showed similar growth characteristic and fatty acid compositions. Our data further identified that fabV conferred Xaj with tolerance to various environmental stresses. Although XajFabV conferred Xaj with triclosan resistance, the resistance of Xaj was weaker than that found for Pseudomonas aeruginosa. Moreover, triclosan exhibited a control effect against infection of the Δ fabV/EcfabI to its host walnut. This study revealed the function of XajFabV and laid a theoretical foundation for the fatty acid synthesis mechanism of Xaj.
Fluid Intake in Critically Ill Patients: The “Save Useless Fluids For Intensive Resuscitation” Multicenter Prospective Cohort Study*
Authors: Schortgen Frédérique , Tabra Osorio Cécilia , Carpentier Dorothée , Henry Matthieu , Beuret Pascal , Lacave Guillaume , Simon Georges , Blanchard Pierre-Yves , Gobe Tiphanie , Guillon Antoine , Bitker Laurent , Duhommet Guillaume , Quenot Jean-Pierre , Le Meur Matthieu , Jochmans Sébastien , Dubouloz Fabrice , Mainguy Nolwenn , Saletes Josselin , Creutin Thibault , Nicolas Pierre , Senay Julien , Berthelot Anne-Lise , Rizk Delphine , Tran Van David , Riviere Audrey , Heili-Frades Sarah Beatrice , Nunes Justine , Robquin Nadine , Lhotellier Sylvie , Ledochowski Stanislas , Guénégou-Arnoux Armelle , Constan Adrien ,   Save Useless Fluids For Intensive Resuscitation (SUFFIR) Study Group, Reseau European de Recherche en Ventilation Artificielle (REVA) Network
Published: November 2023

OBJECTIVES:

Patients at risk of adverse effects related to positive fluid balance could benefit from fluid intake optimization. Less attention is paid to nonresuscitation fluids. We aim to evaluate the heterogeneity of fluid intake at the initial phase of resuscitation.

DESIGN:

Prospective multicenter cohort study.

SETTING:

Thirty ICUs across France and one in Spain.

PATIENTS:

Patients requiring vasopressors and/or invasive mechanical ventilation.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

All fluids administered by vascular or enteral lines were recorded over 24 hours following admission and were classified in four main groups according to their predefined indication: fluids having a well-documented homeostasis goal (resuscitation fluids, rehydration, blood products, and nutrition), drug carriers, maintenance fluids, and fluids for technical needs. Models of regression were constructed to determine fluid intake predicted by patient characteristics. Centers were classified according to tertiles of fluid intake. The cohort included 296 patients. The median total volume of fluids was 3546 mL (interquartile range, 2441–4955 mL), with fluids indisputably required for body fluid homeostasis representing 36% of this total. Saline, glucose-containing high chloride crystalloids, and balanced crystalloids represented 43%, 27%, and 16% of total volume, respectively. Whatever the class of fluids, center of inclusion was the strongest factor associated with volumes. Compared with the first tertile, the difference between the volume predicted by patient characteristics and the volume given was +1.2 ± 2.0 L in tertile 2 and +3.0 ± 2.8 L in tertile 3.

CONCLUSIONS:

Fluids indisputably required for body fluid homeostasis represent the minority of fluid intake during the 24 hours after ICU admission. Center effect is the strongest factor associated with the volume of fluids. Heterogeneity in practices suggests that optimal strategies for volume and goals of common fluids administration need to be developed.
Evaluation of the Rothman Index in Predicting Readmission after Colorectal Resection
Authors: Peterson Kent J. , O’Donnell Carly M. , Eastwood Daniel C. , Szabo Aniko , Hu Katherine Y. , Ridolfi Timothy J. , Ludwig Kirk A. , Peterson Carrie Y.
Published: November 2023

The Rothman Index (RI) is a real-time health indicator score that has been used to quantify readmission risk in several fields but has never been studied in gastrointestinal surgery. In this retrospective single-institution study, the association between RI scores and readmissions after unplanned colectomy or proctectomy was evaluated in 427 inpatients. Patient demographics and perioperative measures, including last RI, lowest RI, and increasing/decreasing RI score, were collected. In the selected cohort, 12.4% of patients were readmitted within 30 days of their initial discharge. Last RI, lowest RI, decreasing RI, and increasing RI scores remained significant after controlling for covariates in separate multivariate regression analyses. The last RI score at the time of discharge was found to be the most strongly associated with 30-day readmission risk following colorectal resection. These findings support the RI as a potential tool in the inpatient management of postoperative patients to identify those at high risk of readmission.
Effect of a Performance Feedback Dashboard on Hospitalist Laboratory Test Utilization
Authors: McCormick Caroline , Ahluwalia Sarvpreet , Segon Ankur
Published: November 2023

Background:

Healthcare spending continues to be an area of improvement across all forms of medicine. Overtreatment or low-value care, including overutilization of laboratory testing, has an estimated annual cost of waste of $75.7–$101.2 billion annually. Providing performance feedback to hospitalists has been shown to be an effective way to encourage the practice of quality-improvement-focused medicine. There remains limited data regarding the implementation of performance feedback and direct results on hospital laboratory testing spending in the short term.

Objective:

The objective of this project was to identify whether performance-based feedback on laboratory utilization between both hospitalists and resident teams results in more conservative utilization of laboratory testing.

Design, Setting, Participants:

This quality improvement project was conducted at a tertiary academic medical center, including both direct-care and house-staff teams.

Intervention or Exposure:

A weekly performance feedback report was generated and distributed to providers detailing laboratory test utilization by all hospitalists in a ranked system, normalized by the census of patients, for 3 months.

Main Outcomes and Measures:

The outcome measure was cumulative laboratory utilization during the intervention period compared to baseline utilization during the corresponding 3 months in the year prior and the weekly trend in laboratory utilization over 52 weeks. The aggregate laboratory utilization rate during intervention and control time periods was defined as the total number of laboratory tests ordered divided by the total number of patient encounters. Additionally, the cost difference was averaged per quarter and reported. The week-by-week trend in laboratory utilization was evaluated using a statistical process control (SPC) chart.

Results:

We found that following intervention during January–March 2020, the cumulative complete blood count utilization rate decreased from 5.54 to 4.83 per patient encounter and the basic metabolic panels/CMP utilization rate decreased from 6.65 to 6.11 per patient encounter compared with January–March 2019. This equated to cost savings of ~$42,700 in total for the quarter. Nonrandom variation was seen on SPC charts in weekly laboratory utilization rates for common laboratory tests during the intervention period.

Conclusions:

We found that our intervention did result in a decrease in laboratory test utilization rates across direct-care and house-staff teams. This study lays promising groundwork for one tool that can be used to eliminate a source of hospital waste and improve the quality and efficiency of patient care.
IDEAL PICU Rounds: Improving Daily Efficiency by Applying Lean Principles
Authors: Cagle William Edward , Bagwell Kacy Bennett , Poisson Margaret Oates , Petro Amy Marien , Verdone Kaitlin
Published: November 2023

The objective of this project was to improve communication, patient throughput, and rounding efficiency. Primary outcome studied was transfer/discharge order entry time and secondary outcomes included medication order entry time, staff perception, and time spent per patient. The location was a level one pediatric intensive care unit in an academic children’s hospital. Utilizing Lean Six methodologies the major contributor to increased variability was different attending physician rounding patterns. These patterns were evaluated by a multidisciplinary committee, and the most efficient was adopted by all attending physicians during the study period. Data was collected by secret observers and a pre-post staff perception survey. Transfer/discharge order entry improved by 45 minutes/patient. Medication order entry improved by 89 minutes/order. Staff survey showed increased satisfaction in 9 of 12 aspects. Time spent per patient increased by 20%. In conclusion, standardization of rounds improved patient throughput, medication order entry, and staff satisfaction while increasing value-added time during rounds.
Self-reported Cardiovascular Disease in Career Firefighters With and Without World Trade Center Exposure
Authors: Mueller Alexandra K. , Cohen Hillel , Singh Ankura , Webber Mayris P. , Hall Charles B. , Prezant David J. , Zeig-Owens Rachel
Published: November 2023

Objective

To assess the effect of World Trade Center (WTC) exposure on cardiovascular disease (CVD) in career firefighters.Methods:Firefighters from four US cities completed health questionnaires that provide information about demographics, CVD diagnoses, and CVD risk factors. Firefighters were also compared with respondents of the 2019 National Health Interview Survey.Results:Greater WTC exposure was positively associated with combined coronary artery disease, myocardial infarction, and angina (termed “CAD”) when comparing WTC-exposed with non-WTC–exposed firefighters. Compared with the National Health Interview Survey population, firefighters had lower odds of CAD and stroke.Conclusions:An occupationally appropriate comparison is important to mitigate potential bias from the healthy worker effect. While the risk of CVD in WTC-exposed and non-WTC–exposed firefighters was significantly lower than a general US population, we observed an exposure gradient where greater WTC exposure was associated with greater odds of CVD.
Postresuscitation management
Authors: Behringer Wilhelm , Skrifvars Markus B. , Taccone Fabio Silvio
Published: November 2023

Purpose of review

To describe the most recent scientific evidence on ventilation/oxygenation, circulation, temperature control, general intensive care, and prognostication after successful resuscitation from adult cardiac arrest.

Recent findings

Targeting a lower oxygen target (90–94%) is associated with adverse outcome. Targeting mild hypercapnia is not associated with improved functional outcomes or survival. There is no compelling evidence supporting improved outcomes associated with a higher mean arterial pressure target compared to a target of >65 mmHg. Noradrenalin seems to be the preferred vasopressor. A low cardiac index is common over the first 24 h but aggressive fluid loading and the use of inotropes are not associated with improved outcome. Several meta-analyses of randomized clinical trials show conflicting results whether hypothermia in the 32–34°C range as compared to normothermia or no temperature control improves functional outcome. The role of sedation is currently under evaluation. Observational studies suggest that the use of neuromuscular blockade may be associated with improved survival and functional outcome. Prophylactic antibiotic does not impact on outcome. No single predictor is entirely accurate to determine neurological prognosis. The presence of at least two predictors of severe neurological injury indicates that an unfavorable neurological outcome is very likely.

Postresuscitation care aims for normoxemia, normocapnia, and normotension. The optimal target core temperature remains a matter of debate, whether to implement temperature management within the 32–34°C range or focus on fever prevention, as recommended in the latest European Resuscitation Council/European Society of Intensive Care Medicine guidelines Prognostication of neurological outcome demands a multimodal approach.
Successful management of a giant retroperitoneal ancient schwannoma mimicking malignant tumors: A case report and literature review
Authors: Zaresharifi Nooshin , Karimzadhagh Sahand , Ebrahimian Ramin , Reihanian Zoheir , Abbaspour Elahe , Karimian Paridokht , Taheri Talesh Jouan
Published: November 2023

Introduction and Importance:

Schwannomas, originating from Schwann cells surrounding nerve sheaths, tend to be slow-growing. Among these, giant ancient schwannomas are remarkable for their rare occurrence and their capacity for substantial growth and regressive changes. Furthermore, the expansiveness and flexibility of the retroperitoneal space often conceal the symptoms of retroperitoneal schwannomas, leading to delayed diagnosis and allowing these tumors to grow significantly and become large and long-standing before detection.

Case Presentation:

A 24-year-old man presented with left flank pain and a growing abdominal bulge in the left upper quadrant. Computed tomography scan revealed a 15×15×10 cm lytic expansile lesion. Consequently, the encapsulated mass was surgically excised and diagnosed as an ancient retroperitoneal schwannoma through histological and immunohistochemical studies.

Clinical Discussion:

Comprehensive preoperative planning and a multidisciplinary strategy are imperative for the complete excision of schwannomas. These tumors can present diagnostic complexities, particularly due to nuclear atypia and pleomorphism, which might lead to misinterpretation regarding malignancy. Despite the risks associated with percutaneous biopsies, the low mitotic count is a critical diagnostic factor. Our study underscores the consensus that the definitive diagnosis should rely on postoperative histopathological findings, highlighting the importance of accurate assessment.

Conclusion:

Rare giant retroperitoneal ancient schwannomas pose diagnostic challenges due to their rarity, lack of distinct symptoms, and atypical locations. This study presents a successful case and management.
Assessment of open rhinoplasty in correction of secondary nasal deformities associated with congenital anomalies in maxillofacial region
Authors: Hassoun Murad , Sleman Nadim
Published: November 2023

Purpose:

Nasal deformities associated with cleft lip are one of the most difficult nose correction procedures. This study aims at correction of the nasal deformity that occurred after the initial repair of the lip, which was done at an early age, and achieving the best possible results aesthetically and functionally.

Methods:

The sample included patients presenting at the department of oral and maxillofacial surgery in Hospital between 2017-2018. We applied open rhinoplasty technique to correct nasal deformity according to a specific protocol. One year post operation, we analyzed clinical images before and after surgery and compared the results with the ideal normative values within society. Functional results were evaluated and the level of satisfaction of patients aesthetically was determined.

Results:

10 patients aged between 16-35 years old were included in our study. The results showed improvement in the aesthetic aspect of the nose through the correction of the emergence and rotation of the tip of the nose. This technique did not significantly affect the functional results. Therefore the functional results were satisfactory. This technique has achieved good and satisfying results aesthetically and functionally.

Conclusion:

The data collected from this study demonstrates that open rhinoplasty technique in nasal deformities is effective in aesthetic improvement and it presents satisfactory results at the functional level.
Chronic Social and Psychological Stress Impact Select Neuropathologies in the PS19 Mouse Model of Tauopathy
Authors: Lyons Carey E. , Graves Sara I. , Razzoli Maria , Jeganathan Karthik , Mansk Rachel P. , McGonigle Seth , Sabarinathan Nivedita , van Deursen Jan M. , Baker Darren J. , Bartolomucci Alessandro
Published: November 2023

Objective

Despite advances toward understanding the etiology of Alzheimer’s disease (AD), it remains unclear which aspects of this disease are affected by environmental factors. Chronic life stress increases the risk of aging-related diseases including AD. The impact of stress on tauopathies remains understudied. We examined the effects of stress elicited by social (chronic subordination stress [CSS]) or psychological/physical (chronic restraint stress [CRS]) factors on the PS19 mouse model of tauopathy.

Methods

Male PS19 mice (average age, 6.3 months) were randomized to receive CSS or CRS, or to remain as singly housed controls. Behavioral tests were used to assess anxiety-like behaviors and cognitive functions. Immunofluorescence staining and Western blotting analysis were used to measure levels of astrogliosis, microgliosis, and tau burden. Immunohistochemistry was used to assess glucocorticoid receptor expression.

Results

PS19 mice exhibit neuroinflammation (glial fibrillary acidic protein, t tests: p = .0297; allograft inflammatory factor 1, t tests: p = .006) and tau hyperphosphorylation (t test, p = .0446) in the hippocampus, reduced anxiety (post hoc, p = .046), and cognitive deficits, when compared with wild-type mice. Surprisingly, CRS reduced hippocampal levels of both total tau and phospho-tauS404 (t test, p = .0116), and attenuated some aspects of both astrogliosis and microgliosis in PS19 mice (t tests, p = .068–.0003); however, this was not associated with significant changes in neurodegeneration or cognitive function. Anxiety-like behaviors were increased by CRS (post hoc, p = .046). Conversely, CSS impaired spatial learning in Barnes maze without impacting tau phosphorylation or neurodegeneration and having a minimal impact on gliosis.

Conclusions

Our results demonstrate that social or psychological stress can differentially impact anxiety-like behavior, select cognitive functions, and some aspects of tau-dependent pathology in PS19 male mice, providing entry points for the development of experimental approaches designed to slow AD progression.
Knee disarticulation vs. transfemoral amputation after failed transtibial amputation: Surgical outcome and prosthetic fitting in patients with peripheral vascular disease
Authors: Sjödin Lina S. , Ottosson Carin C. , Lapidus Lasse J.
Published: November 2023

Objective:

Our aim was to compare transfemoral amputation (TFA) to knee disarticulation (KD) as a reamputation level after failed transtibial amputation (TTA) in patients with peripheral vascular disease and/or diabetes.

Methods:

We studied 152 patients undergoing reamputation, 86 TFA and 66 KD, after a failed TTA. The primary outcome was reamputation and reoperation, and secondary outcomes were prosthetic fitting and mortality. Logistic regression analyses were performed to identify factors associated with the outcome.

Results:

The reamputation rate was 36% after KD and 15% after TFA (p = 0.004). The multivariable analysis showed that TFA was associated with a significantly reduced risk of reamputation, odds ratio (OR) = 0.31 (95% confidence interval [95% CI], 0.1–0.7). The overall reoperation rate was 38% after KD and 22% after TFA (p = 0.03). This reduction of risk for TFA was not significant in the multivariable analysis, OR = 0.49 (95% CI, 0.2–1.0). Prosthetic limb fitting was possible in 30% after KD and 19% after TFA (p = 0.1). Previous amputation in the contralateral leg was the only factor associated with reduced ability for prosthetic fitting in the multivariable analysis, OR = 0.15 (95% CI, 0.03–0.7). Mortality at 30 d was 17% and 53% at 1 year. No independent factors affected 30-d mortality in the multivariable analysis.

Conclusions:

In this study, we found a significantly lower risk of reamputation after TFA compared with KD after a failed TTA. We consider TFA to be the reamputation level of choice, especially when there is a need of reducing risk of further reamputations.
Cx43 can form functional channels at the nuclear envelope and modulate gene expression in cardiac cells
Authors: Martins-Marques Tania , Witschas Katja , Ribeiro Ilda , Zuzarte Mónica , Catarino Steve , Ribeiro-Rodrigues Teresa , Caramelo Francisco , Aasen Trond , Carreira Isabel Marques , Goncalves Lino , Leybaert Luc , Girao Henrique
Published: November 2023

Classically associated with gap junction-mediated intercellular communication, connexin43 (Cx43) is increasingly recognized to possess non-canonical biological functions, including gene expression regulation. However, the mechanisms governing the localization and role played by Cx43 in the nucleus, namely in transcription modulation, remain unknown. Using comprehensive and complementary approaches encompassing biochemical assays, super-resolution and immunogold transmission electron microscopy, we demonstrate that Cx43 localizes to the nuclear envelope of different cell types and in cardiac tissue. We show that translocation of Cx43 to the nucleus relies on Importin-β, and that Cx43 significantly impacts the cellular transcriptome, likely by interacting with transcriptional regulators.
In vitro
patch-clamp recordings from HEK293 and adult primary cardiomyocytes demonstrate that Cx43 forms active channels at the nuclear envelope, providing evidence that Cx43 can participate in nucleocytoplasmic shuttling of small molecules. The accumulation of nuclear Cx43 during myogenic differentiation of cardiomyoblasts is suggested to modulate expression of genes implicated in this process. Altogether, our study provides new evidence for further defining the biological roles of nuclear Cx43, namely in cardiac pathophysiology.
Evaluating the effects of moonlight on the vertical flight profiles of three western palaearctic swifts
Authors: Hufkens Koen , Meier Christoph M. , Evens Ruben , Paredes Josefa Arán , Karaardiç Hakan , Vercauteren Stef , Van Gysel Ann , Fox James W. , Pacheco Carlos Miguel , da Silva Luis P. , Fernandes Sandra , Henriques Pedro , Elias Gonçalo , Costa Luís T. , Poot Martin , Kearsley Lyndon
Published: November 2023

Recent studies have suggested the presence of moonlight mediated behaviour in avian aerial insectivores, such as swifts. Here, we use the combined analysis of state-of-the-art activity logger data across three swift species, the common, pallid and alpine swifts, to quantify flight height and activity in responses to moonlight-driven crepuscular and nocturnal light conditions. Our results show a significant response in flight heights to moonlight illuminance for common and pallid swifts, i.e. when moon illuminance increased flight height also increased, while a moonlight-driven response is absent in alpine swifts. We show a weak relationship between night-time illuminance-driven responses and twilight ascending behaviour, suggesting a decoupling of both crepuscular and night-time behaviour. We suggest that swifts optimize their flight behaviour to adapt to favourable night-time light conditions, driven by light-responsive and size-dependent vertical insect stratification and weather conditions.
Quantifying the complexity of plant reproductive structures reveals a history of morphological and functional integration
Authors: Leslie Andrew B. , Mander Luke
Published: November 2023

Vascular plant reproductive structures have undoubtedly become more complex through time, evolving highly differentiated parts that interact in specialized ways. But quantifying these patterns at broad scales is challenging because lineages produce disparate reproductive structures that are often difficult to compare and homologize. We develop a novel approach for analysing interactions within reproductive structures using networks, treating component parts as nodes and a suite of physical and functional interactions among parts as edges. We apply this approach to the plant fossil record, showing that interactions have generally increased through time and that the concentration of these interactions has shifted towards differentiated surrounding organs, resulting in more compact, functionally integrated structures. These processes are widespread across plant lineages, but their extent and timing vary with reproductive biology; in particular, seed-producing structures show them more strongly than spore or pollen-producing structures. Our results demonstrate that major reproductive innovations like the origin of seeds and angiospermy were associated with increased integration through greater interactions among parts. But they also reveal that for certain groups, particularly Mesozoic gymnosperms, millions of years elapsed between the origin of reproductive innovations and increased interactions among parts within their reproductive structures.
Paenibacillus spongiae sp. nov. isolated from deep-water marine sponge Theonella swinhoei
Authors: Zhang Mimi , Song Qianqian , Sang Jin , Li Zhiyong
Published: November 2023

A novel bacterial strain, designated as PHS-Z3T, was isolated from a marine sponge belonging to the genus Theonella on the Puerto Galera Deep Monkey, Philippines. Cells of PHS-Z3T were Gram-stain-positive, motile, oxidase- and catalase-positive, white-pigmented, spore-forming, short rods that could grow at 10–40 °C (optimum, 20 °C), pH 6.0–9.5 (optimum, pH 7.5) and with 2–16 % (w/v) NaCl (optimum, 7 %). The 16S rRNA gene sequence of PHS-Z3T showed 97.9 %, 96.7 %, and 96.2 % identities to

Paenibacillus mendelii

C/2T,

Paenibacillus oenotherae

DT7-4T and

Paenibacillus aurantiacus

RC11T, respectively. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that PHS-Z3T formed an independent cluster with

Paenibacillus mendelii

C/2T. The total genome of PHS-Z3T was approximately 7 613 364 bp in size with a DNA G+C content of 51.6 %. The average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between PHS-Z3T and other type strains of species of the genus

Paenibacillus

were 68.0–81.4 % [ANI by blast (ANIb)], 83.0–88.0 % [ANI by MUMmer (ANIm)] and 12.7–32.1 % (dDDH). The dDDH and ANI values were below the standard cut-off criteria for delineation of bacterial species. The percentage of conserved proteins (POCP) values between the genome of PHS-Z3T and those of members of the genus

Paenibacillus

were 39.7–75.7 %, while the average amino acid identity (AAI) values were 55.9–83.7 %. The sole respiratory quinone in the strain was MK-7, and the predominant fatty acids were anteiso-C15 : 0 and C16 : 0. The major polar lipids of PHS-Z3T consisted of diphosphatidylglycerol, phospholipid and phosphatidylglycerol. The characteristic amino acid in the cell wall of PHS-Z3T was diamino heptanoic acid (meso-DAP). On the basis of the molecular, physiological, biochemical and chemotaxonomic features, strain PHS-Z3T represents a novel species of the genus

Paenibacillus

, for which the name Paenibacillus spongiae sp. nov. is proposed, with the type strain PHS-Z3T (=MCCC 1K07848T=KCTC 43443T).
Emendation of Principle 8, Rules 5b, 8, 15, 33a, and Appendix 7 of the International Code of Nomenclature of Prokaryotes to include the categories of kingdom and domain
Authors: Oren Aharon
Published: November 2023

Following an electronic discussion on proposals to emend Principle 8, Rules 5b, 8, 15, 33a, and Appendix 7 of the International Code of Nomenclature of Prokaryotes (ICNP), I here report the outcome of the ballot on these proposals by the members of the International Committee on Systematics of Prokaryotes. These emendations enact the addition of the categories of kingdom and domain to the ICNP.
Relationship between Protein Conformational Stability and Its Immunogenicity When Administering Antigens to Mice Using Adjuvants
Authors: Oyama Kosuke , Ueda Tadashi
Published: November 2023

Antigen-presenting cells (APCs) are crucial in the immune system by breaking down antigens into peptide fragments that bind to major histocompatibility complex molecules. Previous research suggests that stable proteins may hinder CD4+T cell stimulation by impeding antigen processing and presentation. Conversely, some proteins require stabilization to activate the immune response. This discrepancy may be influenced by various factors, including protein characteristics and the use of different adjuvants in animal experiments. Here, we investigated the effects of adjuvants on antigen administration, specifically focusing on the stability of the CH2domain. Together with the previous study, we show that protein stability is also crucial in triggering an immune response in mice by binding protein antigens to B cell receptors on APCs. Together with the study so far, we propose that intrinsic protein stability is crucial for binding to B cell receptors on APCs in mice when administering antigens with adjuvants.
ParabrachialCalcaneurons drive nociplasticity
Authors: Condon Logan F. , Yu Ying , Park Sekun , Cao Feng , Pauli Jordan L. , Nelson Tyler S. , Palmiter Richard D.
Published: November 2023

Pain that persists beyond the time required for tissue healing and pain that arises in the absence of tissue injury are poorly understood phenomena mediated by plasticity within the central nervous system. The parabrachial nucleus (PBN) is a hub that relays aversive sensory information and appears to play a role in nociplasticity. Here, by preventing PBNCalcaneurons from releasing neurotransmitter or directly stimulating them we demonstrate that activation ofCalcaneurons is both necessary for the manifestation of chronic pain after nerve ligation and is sufficient to drive nociplasticity in wild-type mice. Aversive stimuli such as exposure to nitroglycerin, cisplatin, or LiCl can drive nociplasticity in aCalca-neuron-dependent manner. Calcium fluorescence imaging reveals that nitroglycerin activates PBNCalcaneurons and potentiates their responses to mechanical stimulation. The activity and excitability ofCalcaneurons increased for several days after aversive events, but prolonged nociplasticity likely occurs in downstream circuitry.
Drug-Target-Interaction Prediction with Contrastive and Siamese Transformers
Authors: Ikechukwu Daniel , Kumar Arav
Published: November 2023

Abstract

As machine learning (ML) becomes increasingly integrated into the drug development process, accurately predicting Drug-Target Interactions (DTI) becomes a necessity for pharmaceutical research. This prediction plays a crucial role in various aspects of drug development, including virtual screening, repurposing of drugs, and proactively identifying potential side effects. While Deep Learning has made significant progress in enhancing DTI prediction, challenges related to interpretability and consistent performance persist in the field. This study introduces two innovative methodologies that combine Generative Pretraining and Contrastive Learning to specialize Transformers for bio-chemical modeling. These systems are designed to best incorporate cross-attention, which enables a nuanced alignment of multi-representation embeddings. Our empirical evaluation will showcase the effectiveness and interpretability of this proposed framework. Through a series of experiments, we provide compelling evidence of its superior predictive accuracy and enhanced interpretability. The primary objective of this research is not only to contribute to the advancement of novel DTI prediction methods but also to promote greater transparency and reliability within the drug discovery pipeline.
Multiplicative frequency and angular speckle reduction in ultrasound imaging
Authors: Li Yilei , Toyonaga Noah , Jiang James , Cable Alex , Chu Steven
Published: November 2023

Speckle is the major artifact in ultrasound imaging, and it is well-known that speckle can be reduced by compounding (averaging) images taken either at different frequencies or from different angles. By averaging images of a phantom taken over a frequency rangeand a 90° span of angles, the combined speckle reduction is demonstrated to be ~ 9× compared to non-compounded images, while the reduction with frequency or angle averaging resulted in reductions of ~ 3× individually. The rf input to the transducer is altered to vary the sound frequency and the phantom is rotated with respect to the transducer to obtain different imaging angles. Numerical simulations of sound scattered by randomly distributed point scatterers showed quantitative agreement with the experiment. Using a commercial system, a 6× reduction in speckle is demonstrated imaging a human wrist. A robot arm is used to move the transducer along a circular path to acquire images at 9 angles separated by 10°. The commercial system does not allow direct control of the input to the transducer, so the broadband signal detected is Fourier filtered to obtain images at different frequencies with ~ 2× reduced frequency range. Images taken at different angles contain distortions from speed of sound variations and pressure induced by the probe. Two forms of non-rigid image registration are applied to correct for the distortions and create a higher resolution composite image. A design for achieving ~10× speckle reduction with essentially no loss in imaging speed is described.
Pericyte ablation causes hypoactivity and reactive gliosis in adult mice
Authors: Cashion Jake M. , Brown Lachlan S. , Morris Gary P. , Fortune Alastair J. , Courtney Jo-Maree , Cullen Carlie L. , Young Kaylene M. , Sutherland Brad A.
Published: November 2023

Pericytes are contractile cells that enwrap capillaries allowing them to control blood flow, maintain the blood-brain barrier and regulate immune cell trafficking in the CNS. Pericytes are lost or become dysfunctional in neurodegenerative diseases such as Alzheimer’s disease, stroke, and multiple sclerosis, but their role in health and disease is poorly understood. Our aim was to evaluate blood-brain barrier integrity and glial reactivity, and to assess behavioural phenotypes that emerge following pericyte ablation in adult mice. The delivery of tamoxifen toPDGFRβ-CreERT2:: Rosa26-DTAtransgenic mice produced a dose-dependent ablation of pericytes. A single low dose of tamoxifen ablated approximately half of all brain pericytes, and two consecutive daily high doses ablated more than 80% of brain pericytes. To determine whether pericyte ablation could induce a behavioural phenotype, we assessed patterns of voluntary movement, as well as balance and coordination using the open field and beam walk tasks. Mice with ∼50% pericyte loss travelled half the distance and spent half as much time moving in the open field as control mice. Mice with more than 80% pericyte ablation also slipped more frequently in the beam walk task than control mice. In brain cryosections from pericyte-ablated mice, blood vessel structure was unchanged, but lumen area was increased. Pericyte-ablated mice also experienced blood-brain barrier leakage, hypoxia and increased microgliosis and astrogliosis compared to control mice. Our results highlight the importance of pericytes for brain health, as pericyte loss can directly drive brain injury and behavioural alterations in mice.
Reliance on self-reports and estimated food composition data in nutrition research introduces significant bias that can only be addressed with biomarkers
Authors: Ottaviani Javier I. , Sagi-Kiss Virag , Schroeter Hagen , Kuhnle Gunter G. C.
Published: November 2023

The chemical composition of foods is complex, variable, and dependent on many factors. This has a major impact on nutrition research as it foundationally affects our ability to adequately assess actual intake of nutrients and other compounds. Despite of this, accurate data on nutrient intake are key for investigating associations and causal relationships between intake, health, and disease risk at the service of developing evidence-based dietary guidance that enables improvements in population health. Here, we exemplify the importance of this challenge by investigating the impact of food content variability on nutrition research using three bioactives as model: flavan-3-ols, (–)-epicatechin, and nitrate. Our results show that common approaches aimed at addressing the high compositional variability of even the same foods impede the accurate assessment of nutrient intake, generally. This suggests that the results of many nutrition studies using food composition data are potentially unreliable and carry greater limitations than commonly appreciated, consequently resulting in dietary recommendations with significant limitations and unreliable impact on public health. Thus, current challenges related to nutrient intake assessments need to be addressed and mitigated by the development of improved dietary assessment methods involving the use of nutritional biomarkers.
Social Rank Alters the Synchrony of Attribute Integration in Altruistic Decisions
Authors: Ni Yinmei , Li Jian
Published: November 2023

Social rank, which represents the hierarchical dominance structure in societies, forms the backdrop against which most social decisions are made. Effective social decision-making demands the flexible integration of multifaceted information, including the relative weights and timings of different attributes. However, there is limited understanding of the potential impact of attribute timing on social preferences and, crucially, whether attribute weights and timings are susceptible to the influence of social rank. Here, through a two-stage social decision task, we manipulated subjects’ social rank before they engaged in altruistic decisions. By interrogating behavioral data through the lens of the time-varying drift diffusion process, we found that the behavioral patterns are better explained by a model that considers both attribute timing and weight. Interestingly, varying social ranks only modulate attribute timings in the decision process, leaving attribute weights unaffected. Furthermore, we demonstrated that individuals with more prosocial tendencies exhibited higher sensitivities of attribute timing in response to the changes of social rank and these results were replicated in a separate and larger cohort of participants. Our results underscore the intricate interplay between social rank and social attribute integration and introduce a new dimension to the computational mechanisms that underlie social decision-making.

Author Summary

Social rank characterizes the background where most social decisions take place, however, the cognitive and computational mechanisms underlying how social rank influences altruistic decisions remain elusive. Here, combining a two-stage social decision task and time-varying DDM, we reveal that social rank specifically modulates attribute timings in the decision process, leaving attribute weights unaffected. Our results underscore the intricate interplay between social rank and social attribute integration during social decision-making.
Phylogenomics and biogeography of the feather lice (Phthiraptera: Ischnocera) of parrots
Authors: Johnson Kevin P. , Doña Jorge
Published: November 2023

Avian feather lice (Phthiraptera: Ischnocera) have undergone morphological diversification into ecomorphs based on the mechanism for escaping host preening defenses. Parrot lice are one prominent example of this phenomenon, with wing, body, or head louse ecomorphs occurring on various groups of parrots. Currently defined genera of parrot lice typically correspond to this ecomorphological variation. Here we explore the phylogenetic relationships among parrot feather lice by sequencing whole genomes and assembling a target set of 2,395 nuclear protein coding genes. Phylogenetic trees based on concatenated and coalescent analyses of these data reveal highly supported trees with strong agreement between methods of analysis. These trees reveal that parrot feather lice fall into two separate clades that form a grade with respect to theBrueelia-complex. All parrot louse genera sampled by more than one species were recovered as monophyletic. The evolutionary relationships among these lice showed evidence of strong biogeographic signal, which may also be related to the relationships among their hosts.
Hepatocyte-Targeted siTAZ Therapy Lowers Liver Fibrosis in NASH Diet-Fed Chimeric Mice with Hepatocyte-Humanized Livers
Authors: Wang Xiaobo , Moore Mary P. , Shi Hongxue , Miyata Yoshinari , Donnelly Sara K. , Radiloff Daniel R. , Tabas Ira
Published: November 2023

Nonalcoholic steatohepatitis (NASH) is emerging as the most common cause of liver disease. Although many studies in mouse NASH models have suggested therapies, translation to humans is poor, with no approved drugs for NASH. One explanation may lie in inherent differences between mouse and human hepatocytes. We used NASH diet-fed chimeric mice reconstituted with human hepatocytes (hu-liver mice) to test a mechanism-based hepatocyte-targeted siRNA, GalNAc-siTaz, shown previously to block the progression to fibrotic NASH in mice. Mice were reconstituted with human hepatocytes following ablation of endogenous hepatocytes, resulting in ~95% human hepatocyte reconstitution. The mice were then fed a high-fat choline-deficient Lamino acid-defined diet for 6 weeks to induce NASH, followed by six weekly injections of GalNAc-siTAZ to silence hepatocyte-TAZ or control GalNAc-siRNA (GalNAc-control) while still on the NASH diet. The results revealed that GalNAc-siTAZ lowered human hepatic TAZ and IHH, the major TAZ target that promotes liver fibrosis in NASH. Most importantly, GalNAc-siTAZ decreased liver inflammation, hepatocellular injury, hepatic fibrosis, and profibrogenic mediator expression, and profibroticNOTCHvs. GalNAc-control, indicating that GalNAc-siTAZ decreased the progression of NASH in mice reconstituted with human hepatocytes. In conclusion, silencing TAZ in human hepatocytes suppresses liver fibrosis in a hu-liver model of NASH.

Impact and Implications

No drugs have yet been approved for NASH, which is a leading cause of liver disease worldwide. The findings here provide support for this therapeutic strategy of using hepatocyte-targeted siTAZ to decrease NASH progression. More generally, the study illustrates how hu-liver NASH mice can be used to evaluate therapeutic hepatocyte-targeted siRNAs to help prioritize future testing in human NASH.
Age-induced midbrain-striatum assembloids model early phenotypes of Parkinson’s disease
Authors: Barmpa Kyriaki , Saraiva Claudia , Gomez-Giro Gemma , Gabassi Elisa , Spitz Sarah , Brandauer Konstanze , Rodriguez Gatica Juan E. , Antony Paul , Robertson Graham , Papastefanaki Florentia , Kubitscheck Ulrich , Salti Ahmad , Ertl Peter , Matsas Rebecca , Edenhofer Frank , Schwamborn Jens C.
Published: November 2023

Parkinson’s disease (PD), one of the most common aging-associated neurodegenerative disorders, is characterised by nigrostriatal pathway dysfunction, caused by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) of the midbrain and the dopamine depletion in the striatum. State of the art, humanin vitromodels are enabling the study of the dopaminergic neurons’ loss, but not the dysregulation of the dopaminergic network in the nigrostriatal pathway. Additionally, these models do not incorporate aging characteristics which potentially contribute to the development of PD. Therefore, it is conceivable that research conducted using these models overlooked numerous processes that contribute to disease’s phenotypes. Here we present a nigrostriatal pathway model based on midbrain-striatum assembloids with inducible aging. We show that these assembloids are capable of developing characteristics of the nigrostriatal connectivity, with catecholamine release from the midbrain to striatum and synapse formation between midbrain and striatal neurons. Moreover, Progerin-overexpressing assembloids acquire aging traits that lead to early phenotypes of PD. This new model shall help to reveal the contribution of aging as well as nigrostriatal connectivity to the onset and progression of PD.