bluuebunny/crossref_metadata_2025 huggingface dataset:
Debriefing Methods for Simulation in Healthcare
Authors: Duff Jonathan P. , Morse Kate J. , Seelandt Julia , Gross Isabel T. , Lydston Melis , Sargeant Joan , Dieckmann Peter , Allen Joseph A. , Rudolph Jenny W. , Kolbe Michaela
Published: January 2024

Debriefing is a critical component in most simulation experiences. With the growing number of debriefing concepts, approaches, and tools, we need to understand how to debrief most effectively because there is little empiric evidence to guide us in their use. This systematic review explores the current literature on debriefing in healthcare simulation education to understand the evidence behind practice and clarify gaps in the literature. The PICO question for this review was defined as “In healthcare providers [P], does the use of one debriefing or feedback intervention [I], compared to a different debriefing or feedback intervention [C], improve educational and clinical outcomes [O] in simulation-based education?” We included 70 studies in our final review and found that our current debriefing strategies, frameworks, and techniques are not based on robust empirical evidence. Based on this, we highlight future research needs.
Healthcare Simulation Training Guidelines and Literature Reviews From the Third Society for Simulation in Healthcare Research Summit
Authors: Scerbo Mark W.
Published: January 2024

The Society for Simulation in Healthcare held its third research summit in January 2023 with the aim of establishing evidence-based guidelines for healthcare simulation training. A panel of researchers, clinicians, and subject-matter experts conducted reviews of the literature addressing 12 key topics and followed a formal process to generate 16 guidelines for simulation-based training in healthcare. Eleven peer-reviewed literature reviews accompany these guidelines. Over the last 12 years, the Society for Simulation in Healthcare research summits have evolved with a consistent aim to advance simulation research, culminating in the formal set of guidelines published in this special issue.
Incidental but Not Insignificant: Thyroid Cancer in Patients with Graves Disease
Authors: Wang Rongzhi , Disharoon Mitchell , Song Zhixing , Gillis Andrea , Fazendin Jessica , Lindeman Brenessa , Chen Herbert , McMullin Jessica Liu
Published: January 2024

BACKGROUND:

Graves disease is the most common cause of hyperthyroidism in the US. Treatment with antithyroid drugs and radioactive iodine is more commonly used than surgical management with total thyroidectomy (TTx). However, incidentally discovered thyroid cancer (TC) has been described on surgical pathology from patients who underwent surgical treatment of Graves disease, which would be missed with these other treatment strategies. We sought to determine the incidence rate of TC among patients with surgically treated Graves disease.

STUDY DESIGN:

We retrospectively reviewed patients with Graves disease who underwent TTx at a single institution from 2011 to 2023. Pathology reports were reviewed for TC. Patient demographics, preoperative laboratory and radiological evaluations, preoperative medical management, and surgical outcomes were compared between patients with and without incidental TC.

RESULTS:

There were 934 patients, of whom 60 (6.4%) patients had incidentally discovered TC on pathology. The majority (58.3%) of patients had papillary thyroid carcinoma, followed by 33.3% with papillary microcarcinoma. Preoperative ultrasound (US) was obtained in 564 (60.4%) of patients, with 44.3% with nodules, but only 34 (13.7%) of those with nodules had TC on final pathology. Preoperative fine needle aspiration was obtained in 15 patients with TC, and 8 patients (53.3%) were reported as benign lesions, which ultimately had TC on final pathology. There was no difference in sex, race or ethnicity, preoperative medical management, and postoperative outcomes between the 2 groups.

CONCLUSIONS:

Incidental TC was found on surgical pathology in 6.4% of patients undergoing TTx for Graves disease. Preoperative imaging with US and fine needle aspiration were often unreliable at predicting TC. The incidence of TC should not be underestimated when counseling patients on definitive management for Graves disease.
Evaluating the influence of novel charge transport materials on the photovoltaic properties of MASnI
3
solar cells through SCAPS-1D modelling
Authors: Afridi Khalid , Noman Muhammad , Jan Shayan Tariq
Published: January 2024

In recent decades, substantial advancements have been made in photovoltaic technologies, leading to impressive power conversion efficiencies (PCE) exceeding 25% in perovskite solar cells (PSCs). Tin-based perovskite materials, characterized by their low band gap (1.3 eV), exceptional optical absorption and high carrier mobility, have emerged as promising absorber layers in PSCs. Achieving high performance and stability in PSCs critically depends on the careful selection of suitable charge transport layers (CTLs). This research investigates the effects of five copper-based hole transport materials and two carbon-based electron transport materials in combination with methyl ammonium tin iodide (MASnI
3
) through numerical modelling in SCAPS-1D. The carbon-based CTLs exhibit excellent thermal conductivity and mechanical strength, while the copper-based CTLs demonstrate high electrical conductivity. The study comprehensively analyses the influence of these CTLs on PSC performance, including band alignment, quantum efficiency, thickness, doping concentration, defects and thermal stability. Furthermore, a comparative analysis is conducted on PSC structures employing both p-i-n and n-i-p configurations. The highest-performing PSCs are observed in the inverted structures of CuSCN/MASnI
3
/C
60
and CuAlO
2
/MASnI
3
/C
60
, achieving PCE of 23.48% and 25.18%, respectively. Notably, the planar structures of Cu
2
O/MASnI
3
/C
60
and CuSbS
2
/MASnI
3
/C
60
also exhibit substantial PCE, reaching 20.67% and 20.70%, respectively.
Still little evidence sex differences in spatial navigation are evolutionary adaptations
Authors: Hults Connor M. , Francis Richard C. , Clint Edward K. , Smith Winter , Sober Elliott R. , Garland Theodore , Rhodes Justin S.
Published: January 2024

A putative male advantage in wayfinding ability is the most widely documented sex difference in human cognition and has also been observed in other animals. The common interpretation, the sex-specific adaptation hypothesis, posits that this male advantage evolved as an adaptive response to sex differences in home range size. A previous study a decade ago tested this hypothesis by comparing sex differences in home range size and spatial ability among 11 species and found no relationship. However, the study was limited by the small sample size, the lack of species with a larger female home range and the lack of non-Western human data. The present study represents an update that addresses all of these limitations, including data from 10 more species and from human subsistence cultures. Consistent with the previous result, we found little evidence that sex differences in spatial navigation and home range size are related. We conclude that sex differences in spatial ability are more likely due to experiential factors and/or unselected biological side effects, rather than functional outcomes of natural selection.
Nanopore sequencing elucidates in-vivo development of meropenem resistance by insertion of a mobile genetic element in the porin gene ompC in E. coli.
Authors: Matamoros Sébastien , van Hattem Jarne
Published: January 2024

An ESBL-producing E. coli-isolate recovered from a patient undergoing long-term treatment developed resistance to meropenem without acquiring carbapenem-hydrolysing enzymes. We performed Nanopore and Illumina sequencing and subsequent full hybrid genome assembly of this isolate and the meropenem-susceptible isolate recovered almost 8 weeks prior. Whole genome MLST patterns did not differ between isolates. However, we found the insertion of an IS5-like element in the sequence of the ompC gene and an increase in the number of copies of the CTX-M-15 gene in the resistant isolate. These results show that E. coli can develop meropenem resistance under antibiotic pressure by mutations in ompC genes and increasing the copy number of ESBL genes, and the value of next generation sequencing to reveal resistance mechanisms not detected by conventional PCR.
Commercial farmed swine harbour a variety of pathogenic bacteria and antimicrobial resistance genes
Authors: Eiamsam-ang Thanaporn , Tadee Pakpoom , Buddhasiri Songphon , Chuammitri Phongsakorn , Kittiwan Nattinee , Pascoe Ben , Patchanee Prapas
Published: January 2024

Introduction. The northern region of Thailand serves as a crucial area for swine production, contributing to the Thai community food supply. Previous studies have highlighted the presence of foodborne bacterial pathogens originating from swine farms in this region, posing a threat to both human and animal health.

Gap statement. Multiple swine bacterial pathogens have been studied at a species level, but the distribution and co-occurrence of bacterial pathogens in agricultural swine has not been well established.

Aim. Our study employed the intestinal scraping technique to directly examine the bacterial micro-organisms interacting with the swine host.

Methodology. We used shotgun metagenomic sequencing to analyse the bacterial pathogens inhabiting the caecal microbiome of swine from five commercial farms in northern Thailand.

Results. A variety of pathogenic and opportunistic bacteria were identified, including

Escherichia coli

,

Clostridium botulinum

,

Staphylococcus aureus

and the

Corynebacterium

genus. From a One Health perspective, these species are important foodborne and opportunistic pathogens in both humans and agricultural animals, making swine a critical pathogen reservoir that can cause illness in humans, especially farm workers. Additionally, the swine caecal microbiome contains commensal bacteria such as

Bifidobacterium

,

Lactobacillus

and

Faecalibacterium

, which are associated with normal physiology and feed utilization in healthy swine. Antimicrobial resistance genes were also detected in all samples, specifically conferring resistance to tetracycline and aminoglycosides, which have historically been used extensively in swine farming.

Conclusion. The findings further support the need for improved sanitation standards in swine farms, and additional monitoring of agricultural animals and farm workers to reduce contamination and improved produce safety for human consumption.
Ethanol extract of Aster glehni exhibits
anti-inflammatory and anti-oxidant effects in RAW 264.7 cells and
Caenorhabditis elegans
Authors: Seo Mi-Kyung , Chu Han-Na , Lee Da-Bin , Kim Haeng-Ran , Hwang In-Seon , Jeong Yong-Jin , Yoon Sung-Ran , Kang Seok-Seong , Jang Kyeong-A , Kang Min-Sook
Published: January 2024

This study investigated the anti-oxidative and anti-inflammatory effects of
Aster glehni (AG) extract in RAW 264.7 cells and
Caenorhabditis elegans. The total polyphenol and flavonoid
contents were higher in the ethanol extracts than in the hot water extracts. As
a result of measuring the moisture contents (%) and extraction yields
(%) of AG and drying A. glehni for processing (DAG),
70% ethanol, which has the highest percentage of extraction yield, was
selected as the final solvent. DPPH radical scavenging activity showed higher
antioxidant activity of ethanol extracts of DAG than AG. The cytotoxicity assay
of the AG or DAG ethanol extracts was treated at different concentrations (25,
50, and 100 μg/mL), and cell viability rates were higher
than 80% at all concentrations. The LPS-stimulated nitric oxide (NO)
production in RAW 264.7 was significantly reduced at all concentrations of AG
and DAG groups. As a result of measuring the gene expression of iNOS, which
induces NO production, the AG or DAG group decreased by 33% and
32%, compared with the phosphate buffer saline (PBS) group. Under
inflammatory stress conditions, the survival rate of C. elegans treated with AG
or DAG ethanol extract with LPS showed concentration-dependent improvement in
survival rate compared with the PBS group. Considering these results, AG could
potentially be developed as an antioxidant and anti-inflammatory functional food
material.
Monitoring of optimal conditions for producing fermented black
soybeans rich in sulfur-containing amino acids
Authors: Yoon Sung Ran , Lee Jin Ju , Park Jungmin , Ryu Jung A , Nam Ju-Ock , Kang Min Sook , Kim Sun Hwa , Jeong Yong Jin
Published: January 2024

The optimal fermentation conditions for producing fermented black soybeans rich
in sulfur-containing amino acids were investigated. Response surface methodology
monitored fermentation conditions. A central composite design examined the
effect of independent variables: enzyme concentration (X1) and
fermentation time (X2) on yield and methionine content. Both factors
significantly influenced these dependent variables. Enzyme concentration more
profoundly affected amino nitrogen content than fermentation time.
β-Glucan content and cystine level were primarily
affected by fermentation time. We elicited each variable’s regression formula
and identified optimal fermentation conditions for functional compounds. The
predicted optimum conditions were an enzyme concentration of 0.28-0.32%
and a fermentation time of 58.0-62.0 min. Under these optimal conditions, each
black soybean variety's sulfur amino acid content ranged from 818.62 to 922.62
mg/100 g, demonstrating significant variety differences.
Vitamin K variations in conger eel (Conger
myriaster) influenced by harvest time and size
Authors: Park Junhee , Lee Kang-Hee , Templonuevo Rea Mae Cuario , Yang Jinwoo , Chun Jiyeon
Published: January 2024

This study analyzed the variation in vitamin K content in conger eel
(Conger myriaster) caught off Tongyeong, Gyeongsangnam-do,
Korea, focusing on the influence of size (large and small) and harvest period
(monthly throughout 2021). We applied enzymatic extraction and HPLC-fluorescence
methods for the analysis of vitamin K1 (phylloquinone) and
K2 (menaquinone). The vitamin K content in conger eel varied
significantly with size and harvest season (p<0.05). In large-sized
samples, the phylloquinone content peaked in July (0.80±0.09
μg/100 g), while the highest menaquinone content was
in May (0.79±0.11 μg/100 g). Conversely, in
small-sized conger eels, the highest phylloquinone was found in December
(1.94±0.15 μg/100 g), and the peak menaquinone
level was in January (0.66±0.02 μg/100 g). The
fat content was highest in July for large samples and in January for smaller
ones. There was a positive correlation between fat and total vitamin K contents
in conger eel (r=0.631, 0.667). Method validation and quality control measures
ensured data reliability for vitamin K1 and K2 analyses.
This study provides reliable information on the size and seasonal variations of
vitamin K in conger eels, a staple in the Korean diet. This information is
valuable for inclusion in Korea’s national food nutrition database and
for formulating future national health and nutrition policies.
Analysis of the essential oil composition of fresh Panax
ginseng root and identification of novel phenylalkenal
compounds
Authors: Kim Dae-Woon , Kim Young-Hoi , Kim Tae-Young , Choi Han-Suk , Kim Myung-Kon
Published: January 2024

This study investigated the essential oil composition of fresh Panax
ginseng root and identified novel compounds from ginseng oil. The
oil was divided into five fractions (neutral, basic, phenolic, acidic, and
aldehydic). In total, 149 constituents, including 29, 19, and 38 compounds in
the basic, phenolic, and aldehydic fractions, respectively, were identified by
gas chromatography (GC) and GC-mass spectrometry (MS). The primary constituents
of the total ginseng volatile oil were α-humulene
(13.91% as a peak area), bicyclogermacrene (13.59%),
β-caryophyllene (8.24%),
α-neoclovene (7.78%), and
α- and β-panasinsenes
(5.14% and 7.53%). The primary constituents of the basic fraction
were 2-isopropyl-3-methoxypyrazine (35.51%),
3-sec-butyl-2-methoxy-5-methylpyrazine (31.54%),
2-isobutyl-3-methoxypyrazine (8.64%), and 2-methoxy-3-methylpyrazine
(8.40%), whereas in the phenolic fraction, these were benzoic
(25.40%), octanoic (11.57%), nonanoic (9.16%), propionic
(6.35%), and decanoic acids (6.16%). The primary constituents of
the aldehydic fraction were 4-(2-furyl)-3-buten-2-one (23.41%),
benzaldehyde (10.18%), cis-2-heptanal (9.42%),
3-(α-furyl)-propenal (8.51%), and
2-phenyl-2-butenal (7.28%). Among these, the phenylalkenal compounds,
including 2-phenyl-2-butenal, 2-methyl-3-phenyl-2-propenal,
5-methyl-2-phenyl-2-pentenal, 5-methyl-2-phenyl-2-hexenals, 2-phenyl-2-octenal,
and 2-phenyl-2-nonenal, were newly identified in this study as ginseng volatile
constituents. Furthermore, 2-phenyl-2-nonenal was identified as a plant-based
volatile constituent for the first time in this study.
Effect of pretreatment conditions on quality characteristics and
antioxidant activity in pak choi (Brassica rapa L. ssp.
chinensis)
Authors: Choi Jin-Hee , Ahn Hyun-do , Choi Hae-Yeon
Published: January 2024

This study evaluated the impact of blanching pak choi stems and leaves in various
solutions (distilled water, 2% NaCl, and 2% citric acid) at
100°C on their quality characteristics. The highest stem heating loss was
observed in the sodium chloride solution (S-NB) at 15.10%
(p<0.001), and the highest leaf heating loss was in L-NB at 11.44%
(p<0.001). No significant variation was found in the moisture content of
both stems and leaves. Relative to the control, the L value (lightness) of the
stem decreased while the b value (yellowness) increased (p<0.05). In the
leaves, the a value (redness/greenness) and b value increased in L-CB, whereas
they decreased in other groups (p<0.05). S-NB exhibited the highest true
retention (TR) of total polyphenol content (TPC) in stems (p<0.01) and
the highest TR of total flavonoid content (TFC) as well (p<0.001). For
leaves, the highest TR of TPC and TFC was in L-WB (p<0.001). In terms of
antioxidant activity, S-NB in stems and L-WB in leaves showed the highest
scavenging activity measured by DPPH and ABTS+ assays
(p<0.001). Microorganisms were absent in all pretreatment groups but
present in the control. The results suggest that blanching pak choi stems in
2% NaCl solution and leaves in water optimally preserves biologically
active compounds and nutrients.
Physicochemical characteristics of hot-water leachate prepared from
persimmon leaf dried after steaming or freezing treatment
Authors: Chung Hun-Sik , Youn Kwang-Sup , Kim Jong-Kuk
Published: January 2024

This study was conducted to develop a preservation technology that can induce
changes in physicochemical properties to effectively utilize of persimmon
leaves. The application effects of steaming or freezing technique were
investigated. Astringent persimmon leaves were steam-blanched (100°C, 30
sec) or frozen (−20°C, 15 d), followed by hot-air drying
(50°C). The physicochemical properties of the extract obtained by
hot-water leaching from the dried leaves were compared. The extract of leaves
dried without pretreatment was used as a control. L* value was higher in
steamed than in control and frozen. a* value was highest in the control.
The browning index was higher in the frozen and lower in the steamed than in the
control. Soluble solids were the highest in the steamed and the lowest in the
frozen. Sucrose content was relatively high in the steamed, and the glucose and
fructose contents were relatively high in the frozen. Total polyphenol content
and DPPH radical scavenging activity were higher in steamed and lower in frozen
than in control. Thus, it was confirmed that steam or freeze pretreatment after
harvesting persimmon leaves affects the extraction yield, color, antioxidant
capacity and component changes of dried persimmon leaves. Unlike steaming,
freezing pretreatment showed the effect of promoting decomposition and browning
reactions, and it is considered useful when such an effect is needed.
An Integrated Machine Learning Approach Delineates an Entropic Expansion Mechanism for the Binding of a Small Molecule toα-Synuclein
Authors: Menon Sneha , Adhikari Subinoy , Mondal Jagannath
Published: January 2024

The mis-folding and aggregation of intrinsically disordered proteins (IDPs) such asα-synuclein (αS) underlie the pathogenesis of various neurodegenerative disorders. However, targetingαS with small molecules faces challenges due to its lack of defined ligand-binding pockets in its disordered structure. Here, we implement a deep artificial neural network based machine learning approach, which is able to statistically distinguish fuzzy ensemble of conformational substates ofαS in neat water from those in aqueous fasudil (small molecule of interest) solution. In particular, the presence of fasudil in the solvent either modulates pre-existing states ofαS or gives rise to new conformational states ofαS, akin to an ensemble-expansion mechanism. The ensembles display strong conformation-dependence in residue-wise interaction with the small molecule. A thermodynamic analysis indicates that small-molecule modulates the structural repertoire ofαS by tuning protein backbone entropy, however entropy of the water remains unperturbed. Together, this study sheds light on the intricate interplay between small molecules and IDPs, offering insights into entropic modulation and ensemble expansion as key biophysical mechanisms driving potential therapeutics.
Cerebral Blood Volume Modulates Glymphatic Influx Through Extra-ventricular Cerebrospinal Fluid Volume
Authors: Li Juchen , Liu Xingyue , Bo Binshi , Pei Mengchao , Zhang Kaiwei , Tong Chuanjun , Jiang Ming , Zhang Sheng , Li Yufeng , Cang Jing , Liang Zhifeng , Fang Fang
Published: January 2024

The glymphatic system facilitates waste removal via cerebrospinal fluid (CSF) influx alongside perivascular spaces throughout the brain. Vasomotion, the slow motion of blood vessel (0.1-0.3 Hz), has been found to be one of the driving forces for perivascular clearance, but it is not clear whether more chronical change of vessel diameter, as reflected by macroscopic cerebral blood volume (CBV), has any impact on glymphatic function. Combining multimodal mouse MRI techniques, we investigated the relationship among glymphatic influx, CBV, CSF volume and EEG power under six different conditions (awake, dexmedetomidine, isoflurane, isoflurane/dexmedetomidine, ketamine/xylazine and awake with caffeine). We found dexmedetomidine and caffeine enhanced glymphatic influx, while isoflurane reduced it compared with awake condition. Quantitative CBV imaging revealed that glymphatic influx was negatively correlated to CBV across the above conditions. Furthermore, such negative correlation was found to be mediated in part by changes of extra-ventricular CSF volume, which was quantified using T1 MRI. Taken together, our results suggest that CBV is a consciousness independent modulator of glymphatic function and modulates glymphatic influx through extra-ventricular CSF volume. This new finding opens potential avenues to enhance brain waste clearance by regulating CBV, which could be beneficial for protein deposition related neurological diseases.

Teaser

CBV is a consciousness independent modulator of glymphatic function and modulates glymphatic influx through extra-ventricular CSF volume.
Immunoinformatic approach to design CTL epitope based chimeric vaccine targeting multiple serotypes of dengue virus
Authors: Manocha Nilanshu , Kumar Prashant , Khanna Madhu
Published: January 2024

The dengue outbreak is one of the serious global public health concerns. The World Health Organization reported 3,80,171 cases and 113 deaths this year till March 2023, and the rate of infection is expected to increase in vulnerable parts of the world. The development of vaccines is the best approach to managing infectious diseases. All the approved vaccines against dengue are based on live-attenuated virus but they have been questioned for their effectiveness in some population categories. Additionally, random occurrence of four closely related serotypes of dengue virus in humans leading to antibody-dependent enhancement of the disease is yet another cause of vaccine ineffectiveness. Therefore, development of a therapeutic subunit-vaccine based on epitopes from all four serotypes may be expected to provide effective cross-protective cellular immunity. Towards this end, we designed a multi-epitope chimeric immunogen using envelop protein of dengue virus. The MHC-I binding T-cell epitopes were predicted based on their immunogenicity, allergenicity and antigenicity. NetMHCpan-EL4.1 prediction method was used to determine the binding ability of the epitopes with HLA alleles with population coverage of over 99%. The five most potent epitopes based on their immunogenicity, population coverage and prediction scores were selected for each serotype and a multi-epitope polypeptide was generated by merging peptides with AAY linker. The polypeptide was predicted to be an antigen and a non-allergen with a stable tertiary structure retaining a half-life of 4.4 hours in mammalian system. The polypeptide has the potential to elicit effective cellular immune response against all the dengue virus serotypes.
When the pen is mightier than the sword: semi-automatic 2 and 3D image labelling
Authors: Hollandi Réka , Bauer David , Diosdi Akos , Schrettner Bálint , Toth Timea , Hirling Dominik , Hollandi Gábor , Harmati Maria , Molnár József , Horvath Peter
Published: January 2024

Data is the driving engine of learning-based algorithms, the creation of which fundamentally determines the performance, accuracy, generalizability and quality of any model or method trained on it. When only skilled or trained personnel can create reliable annotations, assisted software solutions are desirable to reduce the time and effort the expert must spend on labelling. Herein is proposed an automated annotation helper software package in napari that offers multiple methods to assist the annotator in creating object-based labels on 2D or 3D images.
Origin and evolutionary trajectories of brown algal sex chromosomes
Authors: Barrera-Redondo Josué , Lipinska Agnieszka P. , Liu Pengfei , Dinatale Erica , Cossard Guillaume , Bogaert Kenny , Hoshino Masakazu , Craig Rory J. , Avia Komlan , Leiria Goncalo , Avdievich Elena , Liesner Daniel , Luthringer Rémy , Godfroy Olivier , Heesch Svenja , Nehr Zofia , Brillet-Guéguen Loraine , Peters Akira F. , Hoarau Galice , Pearson Gareth , Aury Jean-Marc , Wincker Patrick , Denoeud France , Cock J Mark , Haas Fabian B. , Coelho Susana M
Published: January 2024

Sex chromosomes fall into three classes: XX/XY, ZW/ZZ and U/V systems. The rise, evolution and demise of U/V systems has remained an evolutionary enigma. Here, we analyse genomes spanning the entire brown algal phylogeny to decipher their sex-determination evolutionary history. U/V sex chromosomes emerged between 450 and 224 million years ago, when a region containing the pivotal male-determinantMINlocated in a discrete region in proto-U and proto-V chromosomes ceased recombining. Over time, nested inversions led to step-wise expansions of the sex locus, accompanying increasing morphological complexity and sexual differentiation of brown seaweeds. Unlike XX/XY and ZW/ZZ, brown algal U/V evolve mainly by gene gain, showing minimal degeneration. They are structurally dynamic and act as genomic ‘cradles’ fostering the birth of new genes, potentially from ancestrally non coding sequences. Our analyses demonstrate that hermaphroditism arose from ancestral males that acquired U-specific genes by ectopic recombination, and that in the transition from a U/V to an XX/XY system, V-specific genes moved down the genetic hierarchy of sex determination. Both events lead to the demise of U and V and erosion of their specific genomic characteristics. Taken together, our findings offer a comprehensive model of U/V sex chromosome evolution.
Host brain environmental influences on transplanted medial ganglionic eminence progenitors
Authors: Paterno Rosalia , Vu Thy , Hsieh Caroline , Baraban Scott C.
Published: January 2024

Interneuron progenitor transplantation can ameliorate disease symptoms in a variety of neurological disorders. This strategy is based on transplantation of embryonic medial ganglionic eminence (MGE) progenitors. Elucidating host brain environment influences on interneuron progenitors as they integrate is critical to optimizing this strategy across different disease states. Here, we systematically evaluated age and brain region influences on survival, migration and differentiation of transplant-derived cells. We find that early postnatal MGE transplantation yields superior survival and more extensive migratory capabilities compared to juvenile or adult. MGE progenitors migrate more widely in cortex compared to hippocampus. Maturation to interneuron subtypes is regulated by age and brain region. MGE progenitors transplanted into dentate gyrus sub-region of early postnatal hippocampus can differentiate into astrocytes. Our results suggest that host brain environment critically regulates survival, spatial distribution and maturation of MGE-derived interneurons following transplantation. These findings inform and enable optimal conditions for interneuron transplant therapies.
The preoptic Kisspeptin/nNOS/GnRH (KiNG) neuronal network regulates rhythmic LH release through a dual activation-inhibition mechanism
Authors: Delli Virginia , Seux Charles-Antoine , Dehame Julien , Nair Sooraj , Lhomme Tori , Chachlaki Konstantina
Published: January 2024

Gonadotropin-releasing hormone (GnRH) neurons are the final common target of a complex network of cells cooperating for the central control of reproduction. The balance between excitatory and inhibitory transsynaptic and non-synaptic inputs is crucial for the maintenance of the GnRH rhythms: the pulse and the surge. The precise mechanisms behind this remain under debate. In this work, we challenge the hypothesis that excitatory and inhibitory inputs from kisspeptin and neuronal nitric oxide (NO) synthase (nNOS)-expressing neurons orchestrates GnRH release, in a microcircuit that we call the Kisspeptin/nNOS/GnRH (KiNG) neuronal network. Our work specifically focuses on the role of nNOS neurons located in the organum vasculosum laminae terminalis (OV) and the median preoptic nucleus (MePO). nNOS and kisspeptin neurons interact anatomically and functionally, with the kisspeptin receptor (Kiss1r) being differentially regulated in nNOS-expressing neurons across the female estrous cycle. Using a novel viral tool allowing for the measurement of NO/cGMP levels with exquisite sensitivity, we demonstrate that kisspeptin is able to induce NO-dependent cGMP production in the OV/MePO, including in GnRH neuronsin vivo. Using electrophysiological, genetic, chemogenetic and pharmacologic approaches, we reveal that NO production from nNOS neurons in the OV/MePO is needed to fine-tune the GnRH/LH response to kisspeptin, and specifically to turn off GnRH release, thus generating pulses. Our findings provide valuable insights into the tripartite KiNG neuronal network governing the regulation of the GnRH/LH pulse and surge.
Applying gradient tree boosting to QTL mapping with Shapley additive explanations
Authors: Ishibashi Tomohiro , Onogi Akio
Published: January 2024

Mapping quantitative trait loci (QTLs) is one of the major goals of quantitative genetics; however, identifying the interactions between QTLs (i.e., epistasis) remains challenging. Recently developed machine learning methods, such as deep learning and gradient boosting, are transforming the real world. These methods could advance QTL mapping methodologies because of their high capability for capturing complex relationships among features. One problem with applying such complex models to QTL mapping is evaluation of feature importance. In this study, XGBoost, a popular gradient tree boosting algorithm, was applied for QTL mapping in biparental populations with Shapley additive explanations (SHAPs). SHAP is a local (i.e., instance-wise) importance index with the desired properties as feature importance indices. The SHAP-assisted XGBoost (SHAP-XGB) was compared with conventional methods, including composite interval mapping (CIM), multiple interval mapping (MIM), inclusive CIM (ICIM), and BayesC, using simulations and rice heading date data. SHAP-XGB performed comparable to CIM, MIM, ICIM, and BayesC in mapping main QTL effects and was superior to MIM, ICIM, and BayesC in mapping QTL interaction effects. As SHAP can evaluate local importance, interactions between markers can be visualized by plotting SHAP interaction values for each instance (plant/line). These results illustrated the strength of SHAP-XGB in detecting and interpreting epistatic QTLs and suggest the possibility that SHAP-XGB complements conventional methods.
Development and characterization of phospho-ubiquitin antibodies to monitor PINK1-PRKN signaling in cells and tissue
Authors: Watzlawik Jens O. , Hou Xu , Richardson Tyrique , Lewicki Szymon L. , Siuda Joanna , Wszolek Zbigniew K. , Cook Casey N. , Petrucelli Leonard , DeTure Michael , Dickson Dennis W. , Antico Odetta , Muqit Miratul M. K. , Fishman Jordan B. , Pirani Karima , Kumaran Ravindran , Polinski Nicole K. , Fiesel Fabienne C. , Springer Wolfdieter
Published: January 2024

The selective removal of dysfunctional mitochondria, a process termed mitophagy, is critical for cellular health and impairments have been linked to aging, Parkinson disease, and other neurodegenerative conditions. A central mitophagy pathway is orchestrated by the ubiquitin (Ub) kinase PINK1 together with the E3 Ub ligase PRKN/Parkin. The decoration of damaged mitochondrial domains with phosphorylated Ub (p-S65-Ub) mediates their elimination though the autophagy system. As such p-S65-Ub has emerged as a highly specific and quantitative marker of mitochondrial damage with significant disease relevance. Existing p-S65-Ub antibodies have been successfully employed as research tools in a range of applications including western blot, immunocytochemistry, immunohistochemistry, and ELISA. However, physiological levels of p-S65-Ub in the absence of exogenous stress are very low, therefore difficult to detect and require reliable and ultrasensitive methods. Here we generated and characterized a collection of novel recombinant, rabbit monoclonal p-S65-Ub antibodies with high specificity and affinity in certain applications that allow the field to better understand the molecular mechanisms and disease relevance of PINK1-PRKN signaling. These antibodies may also serve as novel diagnostic or prognostic tools to monitor mitochondrial damage in various clinical and pathological specimens.
Decline of honeybees and its consequences for beekeepers and crop pollination in western Nepal
Authors: Kortsch S. , Timberlake T.P. , Cirtwill A.R. , Sapkota S. , Rokaya M. , Devkota K. , Roslin T. , Memmott J. , Saville N.
Published: January 2024

Pollination service by insects is globally threatened, yet trends outside of Europe and North America are poorly understood. Therefore, in less-studied regions of the world, beekeeper records can provide valuable insights into changes in pollinator populations.

We conducted a questionnaire survey of 116 beekeepers in 10 villages in the Jumla District of western Nepal, where the native honeybeeApis cerana ceranais widely kept as a managed honeybee. We complemented the beekeeper survey with field data on insect-crop visitation, a household income survey, and an interview with a local lead beekeeper.

76% of beekeepers reported declines in theApis cerana ceranapopulation. 86% experienced declines in honey yield per hive, and 78% reported declines in the number of beehives per beekeeper. Honey yield per hive fell by 50% between 2012 and 2022, whilst the number of occupied hives decreased by 44%. Beekeepers ranked climate change and declining flower abundance as the most-important drivers of the decline.

The drastic bee declines raise concerns for the future food and economic security of this region, where honey sales contribute to 16% of total household farming income.Apis cerana ceranaplays a major role in crop pollination and contributes more than 50% of all flower visits to apple, cucumber, and pumpkin.

To mitigate further declines in this region, we promote the use of pollinator-friendly farming practices including more wild flowers and maintenance of native habitat areas, and well-insulated log or top-bar log hives to buffer bees against extreme temperature fluctuations, which are expected to worsen with climate warming.
Influence of bacterial swimming and hydrodynamics on infection by phages
Authors: Lohrmann Christoph , Holm Christian , Datta Sujit S.
Published: January 2024

Bacteriophages (“phages”) are viruses that infect bacteria. Since they do not actively self-propel, phages rely on thermal diffusion to find target cells—but can also be advected by fluid flows, such as those generated by motile bacteria themselves in bulk fluids. How does the flow field generated by a swimming bacterium influence how it encounters and is infected by phages? Here, we address this question using coupled molecular dynamics and lattice Boltzmann simulations of flagellated bacteria swimming through a bulk fluid containing uniformly-dispersed phages. We find that while swimming increases the rate at which both the cell body and flagellar propeller are infected by phages, hydrodynamic interactions stronglysuppressthis increase at the cell body, but converselyenhancethis increase at the flagellar bundle. Our results highlight the pivotal influence of hydrodynamics on the interactions between bacteria and phages, as well as other diffusible species in microbial environments.
Astrocytic CREB in nucleus accumbens promotes susceptibility to chronic stress
Authors: Holt Leanne M. , Gyles Trevonn M , Parise Eric M. , Minier-Toribio Angelica , Markovic Tamara , Rivera Matthew , Yeh Szu-Ying , Nestler Eric J.
Published: January 2024

Background

Increasing evidence implicates astrocytes in stress and depression in both rodent models and human Major Depressive Disorder (MDD). Despite this, little is known about the transcriptional responses to stress of astrocytes within the nucleus accumbens (NAc), a key brain reward region, and their influence on behavioral outcomes.

Methods

We used whole cell sorting, RNA-sequencing, and bioinformatic analyses to investigate the NAc astrocyte transcriptome in male mice in response to chronic social defeat stress (CSDS). Immunohistochemistry was used to determine stress-induced changes in astrocytic CREB within the NAc. Finally, astrocytic regulation of depression-like behavior was investigated using viral-mediated manipulation of CREB in combination with CSDS.

Results

We found a robust transcriptional response in NAc astrocytes to CSDS in stressed mice, with changes seen in both stress-susceptible and stress-resilient animals. Bioinformatic analysis revealed CREB, a transcription factor widely studied in neurons, as one of the top-predicted upstream regulators of the NAc astrocyte transcriptome, with opposite activation states seen in resilient versus susceptible mice. This bioinformatic result was confirmed at the protein level with immunohistochemistry. Viral overexpression of CREB selectively in NAc astrocytes promoted susceptibility to chronic stress.

Conclusions

Together, our data demonstrate that the astrocyte transcriptome responds robustly to CSDS and, for the first time, that transcriptional regulation in astrocytes contributes to depressive-like behaviors. A better understanding of transcriptional regulation in astrocytes may reveal unknown molecular mechanisms underlying neuropsychiatric disorders.
AnnoView enables large-scale analysis, comparison, and visualization of microbial gene neighborhoods
Authors: Wei Xin , Tan Huagang , Lobb Briallen , Zhen William , Wu Zijing , Parks Donovan H. , Neufeld Josh D. , Moreno-Hagelsieb Gabriel , Doxey Andrew C.
Published: January 2024

The analysis and comparison of gene neighborhoods is a powerful approach for exploring microbial genome structure, function, and evolution. Although numerous tools exist for genome visualization and comparison, genome exploration across large genomic databases or user-generated datasets remains a challenge. Here, we introduce AnnoView, a web server designed for interactive exploration of gene neighborhoods across the bacterial and archaeal tree of life. Our server offers users the ability to identify, compare, and visualize gene neighborhoods of interest from 30,238 bacterial genomes and 1,672 archaeal genomes, through integration with the comprehensive GTDB and AnnoTree databases. Identified gene neighborhoods can be visualized using pre-computed functional annotations from different sources such as KEGG, Pfam, and TIGRFAM, or clustered based on similarity. Alternatively, users can upload and explore their own custom genomic datasets in GBK, GFF, or CSV format, or use AnnoView as a genome browser for relatively small genomes (e.g., viruses and plasmids). Ultimately, we anticipate that AnnoView will catalyze biological discovery by enabling user-friendly search, comparison, and visualization of genomic data. AnnoView is available athttp://annoview.uwaterloo.ca
Dynamical models reveal anatomically reliable attractor landscapes embedded in resting state brain networks
Authors: Chen Ruiqi , Singh Matthew , Braver Todd S. , Ching ShiNung
Published: January 2024

Analyses of functional connectivity (FC) in resting-state brain networks (RSNs) have generated many insights into cognition. However, the mechanistic underpinnings of FC and RSNs are still not well-understood. It remains debated whether resting state activity is best characterized as noise-driven fluctuations around a single stable state, or instead, as a nonlinear dynamical system with nontrivial attractors embedded in the RSNs. Here, we provide evidence for the latter, by constructing whole-brain dynamical systems models from individual resting-state fMRI (rfMRI) recordings, using the Mesoscale Individualized NeuroDynamic (MINDy) platform. The MINDy models consist of hundreds of neural masses representing brain parcels, connected by fully trainable, individualized weights. We found that our models manifested a diverse taxonomy of nontrivial attractor landscapes including multiple equilibria and limit cycles. However, when projected into anatomical space, these attractors mapped onto a limited set of canonical RSNs, including the default mode network (DMN) and frontoparietal control network (FPN), which were reliable at the individual level. Further, by creating convex combinations of models, bifurcations were induced that recapitulated the full spectrum of dynamics found via fitting. These findings suggest that the resting brain traverses a diverse set of dynamics, which generates several distinct but anatomically overlapping attractor landscapes. Treating rfMRI as a unimodal stationary process (i.e., conventional FC) may miss critical attractor properties and structure within the resting brain. Instead, these may be better captured through neural dynamical modeling and analytic approaches. The results provide new insights into the generative mechanisms and intrinsic spatiotemporal organization of brain networks.

Significance Statement

Our brain remains active even when not engaged in cognitively demanding tasks. However, the processes that determine such ‘resting state’ activity are still not well-understood. Using a large (n > 1000) functional neuroimaging dataset and new techniques for computationally modeling brain activity, we found that the resting brain possesses several distinct mechanisms by which activity can be generated. These mechanisms, or dynamics, vary moment to moment, but result in the activation of similar anatomical regions across different individuals. Our results suggest that the resting brain is neither idle, nor monolithic in its governing mechanisms, but rather possesses a diverse but consistent taxonomy of ways in which it can activate and hence transition to cognitive tasks.
The mechanosensitive Pkd2 channel modulates the recruitment of myosin II and actin to the cytokinetic contractile ring
Authors: Chowdhury Pritha , Sinha Debatrayee , Poddar Abhishek , Chetluru Madhurya , Chen Qian
Published: January 2024

Cytokinesis, the last step in cell division, separate daughter cells through the force produced by an actomyosin contractile ring assembled at the equatorial plane. In fission yeast cells, the ring helps recruit a mechanosensitive ion channel Pkd2 to the cleavage furrow, whose activation by membrane tension promotes calcium influx and daughter cell separation. However, it is unclear how the activities of Pkd2 may affect the actomyosin ring. Here, through both microscopic and genetic analyses of a hypomorphic mutant of the essentialpkd2gene, we examine its potential role in assembling and constricting the contractile ring. Thepkd2-81KDmutation significantly increased the number of type II myosin heavy chain Myo2 (+20%), its regulatory light chain Rlc1 (+37%) and actin (+20%) molecules in the ring, compared to the wild type. Consistent with a regulatory role of Pkd2 in the ring assembly, we identified a strong negative genetic interaction betweenpkd2-81KDand the temperature-sensitive mutantmyo2-E1. Thepkd2-81KD myo2-E1cells often failed to assemble a complete contractile ring. We conclude that Pkd2 modulates the recruitment of type II myosin and actin to the contractile ring, suggesting a novel calcium- dependent mechanism regulating the actin cytoskeletal structures during cytokinesis.
Cbfβ regulates Wnt/β-catenin, Hippo/Yap, and TGFβ signaling pathways in articular cartilage homeostasis and protects from ACLT surgery-induced osteoarthritis
Authors: Chen Wei , Lu Yun , Zhang Yan , Wu Jinjin , McVicar Abigail , Chen Yilin , Zhu Siyu , Zhu Guochun , Lu You , Zhang Jiayang , McConnell Matthew , Li Yi-Ping
Published: January 2024

As the most common degenerative joint disease, osteoarthritis (OA) contributes significantly to pain and disability during aging. Several genes of interest involved in articular cartilage damage in OA have been identified. However, the direct causes of OA are poorly understood. Evaluating the public human RNA-seq dataset showed thatCbfβ,(subunit of a heterodimeric Cbfβ/Runx1,Runx2, or Runx3 complex) expression is decreased in the cartilage of patients with OA. Here, we found that the chondrocyte-specific deletion ofCbfβin tamoxifen-inducedCbfβf/fCol2α1-CreERTmice caused a spontaneous OA phenotype, worn articular cartilage, increased inflammation, and osteophytes. RNA-sequencing analysis showed thatCbfβdeficiency in articular cartilage resulted in reduced cartilage regeneration, increased canonical Wnt signaling and inflammatory response, and decreased Hippo/YAP signaling and TGF-β signaling. Immunostaining and western blot validated these RNA-seq analysis results. ACLT surgery-induced OA decreasedCbfβand Yap expression and increased active β-catenin expression in articular cartilage, while local AAV-mediatedCbfβoverexpression promoted Yap expression and diminished active β-catenin expression in OA lesions. Remarkably, AAV-mediatedCbfβoverexpression in knee joints of mice with OA showed the significant protective effect ofCbfβon articular cartilage in the ACLT OA mouse model. Overall, this study, using loss-of-function and gain-of-function approaches, uncovered that low expression ofCbfβmay be the cause of OA. Moreover, Local admission ofCbfβmay rescue and protect OA through decreasing Wnt/β-catenin signaling, and increasing Hippo/Yap signaling and TGFβ/Smad2/3 signaling in OA articular cartilage, indicating that localCbfβoverexpression could be an effective strategy for treatment of OA.