bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 and Mental Health in China: Effects of Personality and Demographics
Authors: Zhang Xiao , Battisti Michele , Proto Eugenio
Published: January 2023

China was the first country affected by the COVID-19 virus and it reacted strongly in the first months of 2020. This paper presents new evidence on the deterioration in mental health in China between 2018 and 2020. Using two waves of the China Family Panel Studies (CFPS) we can follow the same individuals pre and during the pandemic periods. We find clear evidence of a moderate level of mental health deterioration between 2018 and 2020. The prevalence of severe cases of depression, measured using an eight-item version of the common CES-D scale, increased from 6.33% in 2018 to 7.54% in 2020; quantifiable as around a 19% increase. This deterioration is higher for individuals who are subject to strict lockdowns, about 0.3 symptoms more on average, and it is stronger among those who already reported symptoms of depression in the 2018 wave of data. The effects we find are larger for individuals with more open personalities: one standard deviation of the Openness trait corresponds to 0.08 more symptoms, while more Neurotic individuals do not seem to be more affected. Younger cohorts and individuals with lower levels of education are more affected. Males seem slightly more affected than females, although this difference is statistically non-significant.
Germline loss-of-functionPAMvariants are enriched in subjects with pituitary hypersecretion
Authors: Trivellin Giampaolo , Daly Adrian F. , Hernández-Ramírez Laura C. , Araldi Elisa , Tatsi Christina , Dale Ryan K. , Fridell Gus , Mittal Arjun , Faucz Fabio R. , Iben James R. , Li Tianwei , Vitali Eleonora , Stojilkovic Stanko S. , Kamenicky Peter , Villa Chiara , Baussart Bertrand , Chittiboina Prashant , Toro Camilo , Gahl William A. , Eugster Erica A. , Naves Luciana A. , Jaffrain-Rea Marie-Lise , de Herder Wouter W. , Neggers Sebastian JCMM , Petrossians Patrick , Beckers Albert , Lania Andrea G. , Mains Richard E. , Eipper Betty A. , Stratakis Constantine A.
Published: January 2023

Pituitary adenomas (PAs) are common, usually benign tumors of the anterior pituitary gland which, for the most part, have no known genetic cause. PAs are associated with major clinical effects due to hormonal dysregulation and tumoral impingement on vital brain structures. Following the identification of a loss-of-function variant (p.Arg703Gln) in thePAMgene in a family with pituitary gigantism, we investigated 299 individuals with sporadic PAs and 17 familial isolated pituitary adenomas kindreds forPAMvariants.PAMencodes a multifunctional protein responsible for the essential C-terminal amidation of secreted peptides.

Genetic screening was performed by germline and tumor sequencing and germline copy number variation (CNV) analysis. No germline CNVs or somatic single nucleotide variants (SNVs) were identified. We detected seven likely pathogenic heterozygous missense, truncating, and regulatory SNVs. These SNVs were found in sporadic subjects with GH excess (p.Gly552Arg and p.Phe759Ser), pediatric Cushing disease (c.-133T>C and p.His778fs), or with different types of PAs (c.-361G>A, p.Ser539Trp, and p.Asp563Gly). The SNVs were functionally testedin vitrofor protein expression and trafficking by Western blotting, for splicing by minigene assays, and for amidation activity in cell lysates and serum samples. These analyses confirmed a deleterious effect on protein expression and/or function. By interrogating 200,000 exomes from the UK Biobank, we confirmed a significant association of thePAMgene and rarePAMSNVs to diagnoses linked to pituitary gland hyperfunction.

Identification ofPAMas a candidate gene associated with pituitary hypersecretion opens the possibility of developing novel therapeutics based on altering PAM function.
Frequency and Clinical Characteristics of Breakthrough Cases Post COVID-19 Vaccine and Predictive Risk Factors in College Students
Authors: Abdulrazaq Manal Khudder , Al Redha Jebur Ahmed Abd , Ali Hamdan Baqer Jaafar , Ibrahim Ahmed khalid
Published: January 2023

BACKGROUND

COVID-19 vaccines help protect against infection, severe illness, hospitalization and death. When someone who is vaccinated with either a primary series or a primary series plus a booster dose gets infected with the virus that causes COVID-19, it is referred to as a “vaccine breakthrough infection.”

OBJECTIVES

To assess the frequency and clinical characteristics of breakthrough cases of COVID-19 infection and to study the predictive risk factors.

SUBJECTS&METHODS

A cross-sectional study was carried out including 604 undergraduate medical and non-medical students in Iraq from 10thof August to 29thof September 2022. Data was collected via an online specific questionnaire and analysed to estimate the frequency of COVID-19 breakthrough cases post vaccination, and number of doses of vaccine used. The association of different factors including age, gender, grade, body mass index, smoking, and comorbidities was also studied as predictive risk factors. We used the data to formulate tables, figures and perform statistical tests in IBM SPSS Statistics 25.

RESULTS

Mean age of study sample was 21.78 year ± 3.26 and 339 (56%) were females. In terms of COVID-19 vaccination data, 97 (16%) have received one dose, 459 (76%) two doses and 48 (8%) three doses. Regarding PCR test, 74 (12%) were positive after the first dose compared to 49 (8%) after the second dose. About the symptoms developed, the most frequent were fever in 372 (61.1%), unusual fatigue in 96 (15.79%), chills in 29 (4.77%) and persistent cough in 26 (4.28%). For most predictive factors, results were statistically insignificant.

CONCLUSIONS

In current study; demographic factors showed no statistically significant impact on prevalence of COVID-19 breakthrough cases. Despite this; number of participants who develop symptoms after the second dose of vaccine was high; and having 3 or more symptoms. About half of participants showed symptoms even after being fully vaccinated.
Toxicity-specific peripheral blood T and B cell dynamics in anti-PD-1 and combined immune checkpoint inhibition
Authors: van Eijs Mick J.M. , Verheijden Rik J. , van der Wees Stefanie A. , Nierkens Stefan , van Lindert Anne S.R. , Suijkerbuijk Karijn P.M. , van Wijk Femke
Published: January 2023

Immune checkpoint inhibitors (ICI) have revolutionized the treatment landscape of advanced malignancies, but come with a diverse spectrum of immune-related adverse events (irAEs). Mechanistic studies can aid the transition from expert-opinion to evidence-based irAE treatment strategies. We aimed to longitudinally characterize peripheral blood T and B cell dynamics in ICI-treated patients by multicolor flow cytometry and serum multiplex immunoassay at baseline, ±3 weeks and ±6 weeks or upon clinically relevant irAEs. We analyzed samples from 44 ICI-treated patients (24 anti-PD-1 monotherapy, 20 combined anti-PD-1/anti-CTLA-4; cICI), of whom 21 developed irAEs, and 10 healthy donors. IrAEs after cICI were characterized by significantly enhanced proliferation of Th1-associated, mainly (CD4+) effector memory T cells, as well as Th17-associated immune responses and germinal center activation (reflected by CXCL13 and IL-21 increases). We observed no changes in CD21lo, memory, class-switched or newly activated B cell subsets. Especially double-positive PD-1+LAG-3+CD8+T cells showed enhanced cytotoxic capacity in patients with irAEs after cICI. Within anti-PD-1 monotherapy, irAEs were associated with modestly enhanced Th1-associated responses reflected by increased serum CXCL9 and CXCL10. In conclusion, ICI-induced toxicity is dominated by enhanced Th1-associated responses, but in cICI we also found evidence for Th17-associated responses and germinal center activation. Together, our data add to the growing body of evidence that irAEs may be driven by newly activated CD4+helper T cells, specifically after cICI. This study also supports tailored irAE treatment, based on ICI regimen, and to deploy specific strategies such as Th17 inhibition especially in cICI-associated irAEs.
Elective Surgery Before, During and After the COVID-19 Pandemic in England 2015 - 2022: A Database Study
Authors: Remsing Sandra , Reeves Katharine , Evison Felicity , Morton Dion , Chilton Peter , Bird Paul , Watson Samuel , Khunti Kamlesh , Lilford Richard
Published: January 2023

Objective

To track elective surgery activity before, during and after the COVID-19 pandemic in England. To examine for hypothesised differences in use of independent vs NHS hospitals, and more urgent vs less urgent operations over the pre- and post-COVID time windows.

Design

We extracted data from the Hospital Episodes Statistics database from 1stApril 2015 to 30thApril 2022. This database contains all emergency and elective patient admissions, outpatient appointments and A&E attendances funded by the NHS in England.

Setting

NHS and Independent hospitals in England.

Participants

Adult patients (over 18 years) admitted for elective surgery between April 2015 and April 2022, who were classified as being in priority groups 3 or 4.

Main Outcomes

Total operations, operations by hospital type, and NHS England priority ranking.

Results

The data show that there was a large reduction in the number of elective operations during lockdown with incomplete recovery thereafter. Also the proportion of more urgent surgeries and surgeries in independent hospitals increased in the post-COVID vs pre-COVID time windows.

Conclusion

Under conditions of high-demand, higher value elective surgery procedures are awarded increasing priority and the Independent sector bears a larger share of the load.
Structure and its transformation of elliptical nege-like virus Tanay virus
Authors: Okamoto Kenta , Song Chihong , Sakaguchi Miako , Chalkiadaki Christina , Miyazaki Naoyuki , Nabeshima Takeshi , Morita Kouichi , Inoue Shingo , Murata Kazuyoshi
Published: January 2023

Negeviruses that infect insects are recently identified virus species that are phylogenetically related to several plant viruses. They exhibit a unique virion structure, an elliptical core with a short projection. Negeviruses encode two structural proteins, a glycoprotein that forms a short projection, and an envelope protein that forms an elliptical core. The glycoprotein has been reported only in the negeviruses’ genes, and not in phylogenetically related plant viruses’ genes. In this report, we first describe the three-dimensional electron cryo-microscopy (cryo-EM) structure of Tanay virus (TANAV), one of the nege-like viruses. TANAV particle demonstrates a periodical envelope structure consisting of three layers surrounding the centered viral RNA. The elliptical core dynamically changes its shape under acidic and even low detergent conditions to form bullet-like or tubular shapes. The further cryo-EM studies on these transformed TANAV particles reveal their overall structural rearrangement. These findings suggest putative geometries of TANAV and its transformation in the life cycle, and the potential importance of the short projection for enabling cell entry to the insect hosts.

Impact statement

Negeviridae has recently been declared as a virus family that includes virus species exhibiting a unique particle structure that differs from other known viruses. They are known to be common mosquito viruses isolated around the world, but also phylogenetically related to several plant viruses that impair crop production. Therefore, the negeviruses may also play a role in plant ecosystems that threaten agriculture. However, the mechanism of infection and assembly of the negeviruses as well as their structure were unknown. In this study, intact and dissociated structures of the TANAV were first examined using cryo-EM single particle analysis (SPA) and electron cryo-tomography (cryo-ET). These results reveal new structural geometries of the TANAV particle and its dynamic transformation under acidic and even low-detergent conditions, providing new insights into the infection and assembly mechanism in negeviruses.
The revised reference genome of the leopard gecko (Eublepharis macularius) provides insight into the considerations of genome phasing and assembly
Authors: Pinto Brendan J. , Gamble Tony , Smith Chase H. , Keating Shannon E. , Havird Justin C. , Chiari Ylenia
Published: January 2023

Genomic resources across squamate reptiles (lizards and snakes) have lagged behind other vertebrate systems and high-quality reference genomes remain scarce. Of the 23 chromosome-scale reference genomes across the order, only 12 of the ~60 squamate families are represented. Within geckos (infraorder Gekkota), a species-rich clade of lizards, chromosome-level genomes are exceptionally sparse representing only two of the seven extant families. Using the latest advances in genome sequencing and assembly methods, we generated one of the highest quality squamate genomes to date for the leopard gecko,Eublepharis macularius(Eublepharidae). We compared this assembly to the previous, short-read only,E. maculariusreference genome published in 2016 and examined potential factors within the assembly influencing contiguity of genome assemblies using PacBio HiFi data. Briefly, the read N50 of the PacBio HiFi reads generated for this study was equal to the contig N50 of the previousE. maculariusreference genome at 20.4 kilobases. The HiFi reads were assembled into a total of 132 contigs, which was further scaffolded using HiC data into 75 total sequences representing all 19 chromosomes. We identified that 9 of the 19 chromosomes were assembled as single contigs, while the other 10 chromosomes were each scaffolded together from two or more contigs. We qualitatively identified that percent repeat content within a chromosome broadly affects its assembly contiguity prior to scaffolding. This genome assembly signifies a new age for squamate genomics where high-quality reference genomes rivaling some of the best vertebrate genome assemblies can be generated for a fraction previous cost estimates. This newE. maculariusreference assembly is available on NCBI at JAOPLA010000000. The genome version and its associated annotations are also available via this Figshare repositoryhttps://doi.org/10.6084/m9.figshare.20069273.
StratoMod: Predicting sequencing and variant calling errors with interpretable machine learning
Authors: Dwarshuis Nathan , Tonner Peter , Olson Nathan D. , Sedlazeck Fritz J , Wagner Justin , Zook Justin M.
Published: January 2023

Despite the variety in sequencing platforms, mappers, and variant callers, no single pipeline is optimal across the entire human genome. Therefore, developers, clinicians, and researchers need to make tradeoffs when designing pipelines for their application. Currently, assessing such tradeoffs relies on intuition about how a certain pipeline will perform in a given genomic context. We present Stratomod, which addresses this problem using an interpretable machine-learning classifier to predict variant calling errors in a data-driven manner. We showed Stratomod can precisely quantify the likelihood of missing variants using Hifi or Illumina, and leveraged Stratomod’s interpretability to measure contributions from difficult-to-map and homopolymer regions for each respective outcome. Furthermore, we used Statomod to assess the likelihood of missing variants due to mismapping using linear vs. graph-based references, and identified the hard-to-map regions where graph-based methods excelled and by how much. For these we utilized our new benchmark based on the Q100 HG002 assembly, which contains previously-inaccessible difficult regions. Furthermore, Stratomod presents a new method of finding likely false negatives, which is an improvement over current pipelines which only filter false positives. We anticipate this being useful for performing precise risk-reward analyses when designing variant calling pipelines.
Dopamine D2 receptors in nucleus accumbens cholinergic interneurons increase impulsive choice
Authors: Cavallaro Julianna , Yeisley Jenna , Akdoǧan Başak , Floeder Joseph , Balsam Peter D. , Gallo Eduardo F.
Published: January 2023

Impulsive choice, often characterized by excessive preference for small, short-term rewards over larger, long-term rewards, is a prominent feature of substance use and other neuropsychiatric disorders. The neural mechanisms underlying impulsive choice are not well understood, but growing evidence implicates nucleus accumbens (NAc) dopamine and its actions on dopamine D2 receptors (D2Rs). Because several NAc cell types and afferents express D2Rs, it has been difficult to determine the specific neural mechanisms linking NAc D2Rs to impulsive choice. Of these cell types, cholinergic interneurons (CINs) of the NAc, which express D2Rs, have emerged as key regulators of striatal output and local dopamine release. Despite these relevant functions, whether D2Rs expressed specifically in these neurons contribute to impulsive choice behavior is unknown. Here, we show that D2R upregulation in CINs of the mouse NAc increases impulsive choice as measured in a delay discounting task without affecting reward magnitude sensitivity or interval timing. Conversely, mice lacking D2Rs in CINs showed decreased delay discounting. Furthermore, CIN D2R manipulations did not affect probabilistic discounting, which measures a different form of impulsive choice. Together, these findings suggest that CIN D2Rs regulate impulsive decision-making involving delay costs, providing new insight into the mechanisms by which NAc dopamine influences impulsive behavior.
Incorporating fire-smartness into agricultural policies minimises suppression costs and ecosystem services damages from wildfires
Authors: Lecina-Diaz Judit , Chas-Amil María-Luisa , Aquilué Núria , Sil Ângelo , Brotons Lluís , Regos Adrián , Touza Julia
Published: January 2023

Global climate warming is expected to increase wildfire hazard in many regions of the world. In southern Europe, land abandonment and an unbalanced investment toward fire suppression instead of prevention has gradually increased wildfire risk, which calls for a paradigm change in fire management policies. Here we combined scenario analysis, fire landscape modelling, and economic tools to identify which land-use policies would minimise the expected wildfire-related losses in a representative mountainous area of the northwestern Iberian Peninsula (the Transboundary Biosphere Reserve ‘Gerês-Xurés’, between Spain and Portugal). To do so, we applied the least-cost-plus-net-value-change approach and estimated net changes in wildfire damages based on their implications for the ecosystem services that affect financial returns to landowners in the study area (i.e. agriculture, pasture, and timber) and the wider economic benefits (i.e. recreation and climate regulation) for the 2010-2050 period. Four land-use scenarios were considered: (1) Business as Usual (BAU); (2) fire-smart, fostering more fire-resistant (less flammable) and/or fire-resilient landscapes (fire-smart); (3) High Nature Value farmlands (HNVf), wherein the abandonment of extensive agriculture is reversed; and (4) a combination of HNVf and fire-smart. We found the highest net value change (i.e. the difference between damages and avoided damages) in BAU for timber and pasture provision, and in fire-smart for recreation and climate regulation. HNVf was the best for suppression cost savings, but it generated the lowest expected present value for climate regulation. In fact, the best scenarios related to fire suppression are HNVf and HNVf combined with fire-smart, which also generate the lowest net value change plus net suppression costs in the entire study area (i.e. considering all ecosystem services damages and suppression costs). Therefore, reverting land abandonment through recultivation and promoting fire-resistant tree species is the most efficient way to reduce wildfire hazard. In this sense, payments for ecosystem services should reward farmers for their role in wildfire prevention. This study improves the understanding of the financial and societal benefits derived from reducing fire suppression spending and ecosystem services damage by undertaking fire-smart land-use strategies, which can be essential to enhance local stakeholders’ support for wildfire prevention policies.

Highlights

Land-use changes impact wildfire ecosystem services (ES) damages and suppression costs

Promoting agriculture generates significant suppression cost savings

Agriculture + fire-resistant forests is the best to reduce wildfire ES damages

Land-use policies should balance trade-offs between climate and wildfire regulation

Payments for ES should reward farmers for their role in wildfire prevention
Nutrient-regulated dynamics of chondroprogenitors in the postnatal murine growth plate
Authors: Oichi Takeshi , Kodama Joe , Wilson Kimberly , Tian Hongying , Imamura Yuka , Usami Yu , Oshima Yasushi , Saito Taku , Tanaka Sakae , Iwamoto Masahiro , Otsuru Satoru , Iwamoto-Enomoto Motomi
Published: January 2023

Longitudinal bone growth relies on endochondral ossification in the cartilaginous growth plate where chondrocytes accumulate and synthesize the matrix scaffold that is replaced by bone. The chondroprogenitors in the resting zone maintain the continuous turnover of chondrocytes in the growth plate. Malnutrition is a leading cause of growth retardation in children; however, after recovery from nutrient deprivation, bone growth is accelerated beyond the normal rate, a phenomenon termed catch-up growth. Though nutritional status is a known regulator of long bone growth, it is largely unknown if and how chondroprogenitor cells respond to deviations in nutrient availability. Here, using fate-mapping analysis inAxin2CreERT2mice, we showed that dietary restriction increased the number of Axin2+ chondroprogenitors in the resting zone and simultaneously inhibited their differentiation. Once nutrient deficiency was resolved, the accumulated chondroprogenitor cells immediately restarted differentiation and formed chondrocyte columns, contributing to accelerated growth. Furthermore, we showed that nutrient deprivation reduced the level of phosphorylated Akt in the resting zone, and that exogenous IGF-1 canceled this reduction and stimulated differentiation of the pooled chondroprogenitors, decreasing their numbers. Our study ofAxin2CreERT2revealed that nutrient availability regulates the balance between accumulation and differentiation of chondroprogenitors in the growth plate, and further demonstrated that IGF-1 partially mediates this regulation by promoting the committed differentiation of the chondroprogenitor cells.
Characterizing Mineral Ellipsoids in New Bone Formation at the Interface of Ti6Al4V Porous Implants
Authors: Deering Joseph , Chen Jianyu , Mahmoud Dalia , Tang Tengteng , Lin Yujing , Fang Qiyin , Wohl Gregory R. , Elbestawi Mohamed , Grandfield Kathryn
Published: January 2023

The hierarchy of newly formed bone contains elements of disorder within an ordered multiscale structure, spanning from the macroscale to below the nanoscale. With mineralized structures presenting in the shape of ellipsoids in mature and mineralizing tissue, this work characterizes the heterogeneity in mineral ellipsoid packing at the interface of porous titanium implants. The characterization of mineral at the bone-implant interface offers insight into the osseointegration of titanium implants and the mechanical properties of the interfacial bone tissue. Using scanning transmission electron microscopy and plasma focused ion beam - scanning electron microscopy, mineral ellipsoids are characterized at the implant interface in both 2D and 3D. Heterogeneous in their size and shape within the newly formed bone tissue, ellipsoids are observed with alternating orientations corresponding to unique lamellar packets within 2-3 μm of the titanium implant interface – although this motif is not universal, and a mineral-dense zone can also appear at the implant interface. Short-order ellipsoid orientation shifts are also present in the 3D probe of the implant interface, where an approximate 90° misorientation angle between neighbouring packets of mineral ellipsoid resolves with increasing distance from the titanium, possibly providing a strengthening mechanism to prevent crack propagation in the peri-implant bone.

Graphical Abstract
Sleep specific changes in infra-slow and respiratory frequency drivers of cortical EEG rhythms
Authors: Väyrynen Tommi , Helakari Heta , Korhonen Vesa , Tuunanen Johanna , Huotari Niko , Piispala Johanna , Kallio Mika , Raitamaa Lauri , Kananen Janne , Järvelä Matti , Palva J. Matias , Kiviniemi Vesa
Published: January 2023

Infra-slow fluctuations (ISFs, 0.008-0.1 Hz) characterize hemodynamic and electric potential signals from the human brain. ISFs are known to correlate with the amplitude dynamics of fast (> 1 Hz) neuronal oscillations, and may arise from permeability fluctuations of the blood-brain barrier (BBB). Slow physiological pulsations such as respiration may also influence the amplitude dynamics of fast oscillations, but it remains uncertain if these processes track the fluctuations of fast cortical oscillations or act as their drivers. Moreover, possible effects of sleep and associated BBB permeability changes on such coupling are unknown. Here, we used non-invasive high-density full-band electroencephalography (EEG) in healthy human volunteers (N=21) to measure concurrently the ISFs, respiratory pulsations, and fast neuronal oscillations during periods of wakefulness and sleep, and to assess the strength and direction of their phase-amplitude coupling. The phases of ISFs and respiration were both coupled with the amplitude of fast neuronal oscillations, with stronger ISF coupling evident during sleep. Causality analysis robustly showed that the phase of ISF and respiration drove the amplitude dynamics of fast oscillations in sleeping and waking states. However, the net direction of modulation was stronger during the awake state, despite the stronger power and phase-amplitude coupling of slow signals during sleep. These findings show that the ISFs in slow cortical potentials and respiration together significantly determine the dynamics of fast cortical oscillations. We propose that these slow physiological phases are involved in coordinating cortical excitability, which is a fundamental aspect of brain function.

Significance Statement

Previously disregarded EEG infra-slow fluctuations (0.008-0.1 Hz) and slow physiological pulsations such as respiration have been attracting increasing research interest, which shows that both of these signals correlate with fast (> 1 Hz) neuronal oscillations. However, little has been known about the mechanisms underlying these interactions; for example, the direction of causality in this interaction has not hitherto been studied. Therefore, we investigated full-band EEG in healthy volunteers during wakefulness and sleep to determine if ISF and respiration phases drive neuronal amplitudes. Results showed that ISF and respiration are phase-amplitude coupled, and predict neuronal EEG rhythms. Thus, we conclude that fast neuronal rhythms in human brain are modulated by slower non-neural phenomena.
Performing Roux-N Y Gastric Bypass on Rabbits: Perspective Report to Evaluate Body Weight Changes Food Consumption, And the Malabsorption of Vitamin D3
Authors: Al Meanazel Osaid , Alanazi Fars K. , Hailat Mohammad , Dayyih Wael Abu , Al-Shdefat Ramadan , Assab Mohammad Abu , Awad Riad , Al-Ani Israa , Shakeel Faiyaz , Alshora Doaa H. , Ibrahim Mohamed A.
Published: January 2023

In 1998, Dr. Scopinaro published the first-ever known bariatric surgery, followed by reports by Buchwald and Oien in 2003 and 2013 [1,2]. Bariatric surgery (BS) is the most effective therapy against obesity, and recently it was recommended for type 2 diabetes as a therapeutic plan [3]. BS includes; Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy, and laparoscopic adjustable gastric banding has gained the attention of most healthcare providers in elevation of the issue of obesity for its ease and fast results, especially with patients with mobility problems and those with high risk to develop chronic diseases [1,2]. Gastric bypass is considered the most common BS and a gold standard for weight loss, also known as Roux-en-Y gastric bypass (RYGB). The procedure of this BS is by creating a small pouch of the stomach (300 mL capacity) connected directly to the jejunum by bypassing the duodenum. RYGB has many advantages, such as; the alteration of guts hormones, which reduces appetite and hunger feeling, increases energy expenditure, causes significant long-term weight loss (60-80% of the excess body weight), decreases the amount of food consumed, and preserves 50% of the weight loss during this procedure. However, RYGB has some disadvantages. The most critical issue regarding this BS is altering the absorption of many medicines and nutrients, such as; vitamin D3 (Vit D3) [4,5]. (American Society for Metabolic and Bariatric Surgery. Bariatric Surgery Procedures.https://asmbs.org/patients/bariatric-surgery-procedures(accessed Feb 15, 2020). RYGB was performed on rodents before [6] but was never applied to rabbits. To determine the malabsorption procedure after the RYGB, the pharmacokinetics of the substance must be attained, and data must be calculated, such as; Cmaxand Tmax, to determine the absorption mutation. It was reported that pharmacokinetic studies on rodents could not be accurate due to the erratic absorption of the rodents [7]; thus, many studies have suggested using larger animals, such as rabbits, that do not address the same problem [8]. The current study investigates the ability to perform RYGB on rabbits and tests the effect of the surgery on body weight, food consumption, and the absorption of Vit D3.
Visualization and review of reads alignment on the graphical pan-genome with VAG
Authors: Li Fangping , Hu Haifei , Xiao Zitong , Wang Jingming , Liu Jieying , Zhao Deshu , Fu Yu , Wang Yijun , Yuan Xue , Bu Suhong , Zhou Xiaofan , Zhao Junliang , Wang Shaokui
Published: January 2023

Recent advances in pangenomics have led to the rapid development of graph-based pangenomes that code genetic variant as nodes and edges preserve the contiguity of the sequence and structural variation between individuals. Data visualization is an essential component of genomic data analysis. However, the further application of the graph-based pangenome is still suffered from lacking bioinformatics tools to visualize graph format pangenomes and understand the reads alignment on graph pangenomes. In this research, we developed a novel bioinformatics platform, VAG (Visualizing read alignments in graph genomes), to overcome these challenges. VAG includes multifunctional modules integrated into a single command line and an online visualization platform supported through a web server. This tool can extract specific sequence regions from a graph pangenome and display read alignments on different paths of a graph pangenome. In addition, VAG provides population-level presence/absence variations frequency analysis and sequence path navigation to identify the population differentiation regions. To demonstrate the usage, we investigated genetic variations using a rice graph pangenome with population-level sequencing data to identify important genes and gene clusters underlying theindica–japonicadifferentiation with VAG. After investigating read alignments on the graph pangenome, we identified many false-positive alignments due to TE insertions. To reduce the impact of these misleading alignments, we developed a navigation module to determine and filter those false-positive alignments based on the pair-end alignment information. The utilization of mate-pair information in VAG provides a reliable reference for variation identification. Additionally, we developed a VAG web server to provide a user-friendly and interactive platform to visualize the read alignment data. VAG was also applied to SV discovery in the cucumber and soybean graph-based pangenome and details of VAG can be accessed by the following website (https://ricegenomichjx.xiaomy.net/VAG/sequenceextraction.php).
Causal attribution of agricultural expansion in a small island system using approximate Bayesian computation
Authors: Clark Matt , Andrews Jeffrey , Kolarik Nicholas , Omar Mbarouk Mussa , Hillis Vicken
Published: January 2023

The extent and arrangement of land cover types on our planet directly affects biodiversity, carbon storage, water quality, and many other critical social and ecological conditions at virtually all scales. Given the fundamental importance of land cover, a key mandate for land system scientists is to describe the mechanisms by which pertinent cover types spread and shrink. Identifying causal drivers of change is challenging however, because land systems, such as small-scale agricultural communities, do not lend themselves well to controlled experimentation for logistical and ethical reasons. Even natural experiments in these systems can produce only limited causal inference as they often contain unobserved confounding drivers of land cover change and complex feedbacks between drivers and outcomes. Land system scientists commonly grapple with this complexity by using computer simulations to explicitly delineate hypothesized causal pathways that could have resulted in observed land cover change. Yet, land system science lacks a systematic method for comparing multiple hypothesized pathways and quantifying the probability that a given simulated causal process was in fact responsible for the patterns observed. Here we use a case study of agricultural expansion in Pemba, Tanzania to demonstrate how approximate Bayesian computation (ABC) provides a straightforward solution to this methodological gap. Specifically, we pair an individual-based simulation of land cover change in Pemba with ABC to probabilistically estimate the likelihood that observed deforestation from 2018 to 2021 was driven by soil degradation rather than external market forces. Using this approach, we can show not only how well a specific hypothesized mechanism fits with empirical data on land cover change, but we can also quantify the range of other mechanisms that could have reasonably produced the same outcome (i.e. equifinality). While ABC was developed for use in population genetics, we argue that it is particularly promising as a tool for causal inference for land system science given the wealth of data available in the satellite record. Thus, this paper demonstrates a robust process for identifying the emergent landscape-level signatures of complex social-ecological mechanisms.
Gene networks driven by genetic variation for plasma cortisol in hepatic and adipose tissues implicate corticosteroid binding globulin in modulating tissue glucocorticoid action and cardiovascular risk
Authors: Bankier Sean , Wang Lingfei , Crawford Andrew , Morgan Ruth A , Ruusalepp Arno , Andrew Ruth , Björkegren Johan LM , Walker Brian R , Michoel Tom
Published: January 2023

Genome wide association meta-analyses (GWAMA) by the CORtisol NETwork (CORNET) consortium identified genetic variants spanning theSERPINA6/ SERPINA1locus on chromosome 14 associated with morning plasma cortisol, cardiovascular disease (CVD), andSERPINA6mRNA expression encoding corticosteroid binding globulin (CBG) in liver. These and other findings indicate that higher plasma cortisol levels are causally associated with cardiovascular disease, however, the mechanisms by which variations in CBG lead to CVD are undetermined. Using genomic and transcriptomic data from The Stockholm Tartu Atherosclerosis Reverse Networks Engineering Task (STARNET) study, we identified plasma cortisol linked Single Nucleotide Polymorphisms (SNPs) that are trans-associated with genes from 7 different vascular and metabolic tissues, finding the highest representation of transgenes in liver, subcutaneous adipose and visceral abdominal adipose tissue (FDR = 15%). We identified a sub-set of cortisol-associated trans-genes that are putatively regulated by the Glucocorticoid Receptor (GR), the primary transcription factor activated by cortisol. Using causal inference, we identified GR-regulated trans-genes that are responsible for the regulation of tissue specific gene networks. Cis-expression Quantitative Trait Loci (eQTLs) were used as genetic instruments for identification of pairwise causal relationships from which gene networks could be reconstructed. Gene networks were identified in liver, subcutaneous fat and visceral abdominal fat, including a high confidence gene network specific to subcutaneous adipose (FDR = 10%) under the regulation of the interferon regulatory transcription factor,IRF2. These data identify a plausible pathway through which variation in liver CBG production perturbs cortisol-regulated gene networks in peripheral tissues and thereby promote CVD.
Evidence of phylosymbiosis inFormicaants
Authors: Jackson Raphaella , Patapiou Patapios A. , Golding Gemma , Helanterä Heikki , Economou Chloe K. , Chapuisat Michel , Henry Lee M.
Published: January 2023

Insects share intimate relationships with microbes that play important roles in their biology. Yet our understanding of how host-bound microbial communities assemble and perpetuate over evolutionary time is limited. Ants host a wide range of microbes with diverse functions and are an emerging model for studying the evolution of insect microbiomes. Here, we ask whether phylogenetically related ant species have formed distinct and stable microbiomes. To answer this question, we investigated the microbial communities associated with queens of 14Formicaspecies from five clades, using deep coverage 16S rRNA amplicon sequencing. We reveal thatFormicaspecies and clades harbour highly defined microbial communities that are dominated by four bacteria genera:Wolbachia, Lactobacillus,Liliensternia,andSpiroplasma. Our analysis reveals that the composition ofFormicamicrobiomes mirrors the phylogeny of the host, i.e. phylosymbiosis, in that related hosts harbour more similar microbial communities. Our analysis also revealed significant correlations between microbe co-occurrences, which suggests that synergistic and antagonistic interactions may contribute to the phylosymbiotic signal. Additional factors potentially contributing to the phylosymbiotic signal are discussed, including host phylogenetic relatedness, host-microbe genetic compatibility, modes of transmission, and similarities in host ecologies (e.g., diets). Overall, our results support the growing body of evidence that microbial community composition closely depends on the phylogeny of their hosts, despite bacteria having diverse modes of transmission and localisation within the host.
Mapping cortical excitability in the human dorsolateral prefrontal cortex
Authors: Gogulski Juha , Cline Christopher C. , Ross Jessica M. , Truong Jade , Sarkar Manjima , Parmigiani Sara , Keller Corey J.
Published: January 2023

Objective

To characterize early TEPs anatomically and temporally (20-50 ms) close to the TMS pulse (EL-TEPs), as well as associated muscle artifacts (<20 ms), across the dlPFC. We hypothesized that TMS location and angle influence EL-TEPs, and that EL-TEP amplitude is inversely related to muscle artifact. Additionally, we sought to determine an optimal group-level TMS target and angle, while investigating the potential benefits of a personalized approach.

Methods

In 16 healthy participants, we applied single-pulse TMS to six targets within the dlPFC at two coil angles and measured EEG responses.

Results

Stimulation location significantly influenced EL-TEPs, with posterior and medial targets yielding larger EL-TEPs. Regions with high EL-TEP amplitude had less muscle artifact, and vice versa. The best group-level target yielded 102% larger EL-TEP responses compared to other dlPFC targets. Optimal dlPFC target differed across subjects, suggesting that a personalized targeting approach might boost the EL-TEP by an additional 36%.

Significance

Early local TMS-evoked potentials (EL-TEPs) can be probed without significant muscle-related confounds in posterior-medial regions of the dlPFC. The identification of an optimal group-level target and the potential for further refinement through personalized targeting hold significant implications for optimizing depression treatment protocols.

Highlights

Early local TMS-evoked potentials (EL-TEPs) varied significantly across the dlPFC as a function of TMS target.

TMS targets with less muscle artifact had significantly larger EL-TEPs.

Selection of a postero-medial target increased EL-TEPs by 102% compared to anterior targets.
FGF2-induced Redox Signaling: A Mechanism Regulating Pyruvate Dehydrogenase Driven Histone Acetylation and NANOG Upregulation
Authors: Fojtík Petr , Senfluk Martin , Holomkova Katerina , Salykin Anton , Gregorova Jana , Smak Pavel , Pes Ondrej , Raska Jan , Stetkova Monika , Skladal Petr , Sedlackova Miroslava , Hampl Ales , Bohaciakova Dasa , Uldrijan Stjepan , Rotrekl Vladimir
Published: January 2023

Precise control of pluripotency is a requirement for the safe and effective use of hPSCs in research and therapies. Here we report that pyruvate dehydrogenase upregulates histone H3 pan acetylation and levels of pluripotency marker NANOG in 5% O2. Pyruvate dehydrogenase (PDH) is an essential metabolic switch and a bottleneck for the glycolytic production of acetyl-CoA. Silencing of gene expression showed that PDH is regulated by the activity of its phosphatase PDP1. We show that PDP1 is sensitive to reactive oxygen species-mediated inactivation, leading to the downregulation of H3 pan acetylation and NANOG levels. Furthermore, we show that FGF2, a cytokine commonly used to maintain pluripotency activates pyruvate dehydrogenase through MEK1/2-ERK1/2 signaling pathway-mediated downregulation of ROS in 5% O2, thus promoting histone acetylation. Our results show the importance of pyruvate dehydrogenase in regulating energy metabolism and its connection to pluripotency. Furthermore, our data highlight the role of reactive oxygen species and redox homeostasis in pluripotency maintenance and differentiation.

Highlights

- PDP1-induced activation of PDH leads to increased histone H3 pan acetylation and NANOG levels in hPSCs

- Reactive oxygen species (ROS) inactivate PDP1 and decrease histone H3 pan acetylation and NANOG levels in hPSCs

- MEK1/2-ERK1/2 signaling-mediated downregulation of ROS in 5% O2activates PDH in hPSCs

Graphical abstract
WITHDRAWN: Immunological parameters ofProteus mirabilisisolates in Rheumatoid Arthritis patients with urinary tract infections
Authors: Abdul Fatima Rammadan , Raheem Ihsan Ali , Subhi Hanan Tariq , Fatah Hiwa Ramadhan , Muhammad Hanaa Ali
Published: January 2023

Withdrawal statement

The authors have withdrawn this manuscript because [A conflict of interest exists and needs to correct the data that needs to be re-experimented and rewritten]. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Identification of glioblastoma stem cell-associated lncRNAs using single-cell RNA-sequencing datasets
Authors: Hazra Rasmani , Utama Raditya , Naik Payal , Dobin Alexander , Spector David L.
Published: January 2023

Glioblastoma multiforme (GBM) is an aggressive, heterogeneous grade IV brain tumor. Glioblastoma stem cells (GSCs) initiate the tumor and are known culprits of therapy resistance. Mounting evidence has demonstrated a regulatory role of long non-coding RNAs (lncRNAs) in various biological processes, including pluripotency, differentiation, and tumorigenesis. A few studies have suggested that aberrant expression of lncRNAs is associated with GSCs. However, a comprehensive single-cell analysis of the GSC-associated lncRNA transcriptome has not been carried out. Here, we analyzed recently published single-cell RNA-sequencing datasets of adult human GBM tumors, GBM organoids, GSC-enriched GBM tumors, and developing human brains to identify lncRNAs highly expressed in GBM. To categorize GSC populations in the GBM tumors, we used the GSC marker genes SOX2, PROM1, FUT4, and L1CAM. We found three major GSC population clusters: radial glia, oligodendrocyte progenitor cells, and neurons. We found 10–100 lncRNAs significantly enriched in different GSC populations. We also validated the level of expression and localization of several GSC-enriched lncRNAs using qRT-PCR, single-molecule RNA FISH, and sub-cellular fractionation. We found that the radial glia GSC-enriched lncRNAPANTR1is highly expressed in GSC lines and is localized to both the cytoplasmic and nuclear fractions. In contrast, the neuronal GSC-enriched lncRNAsLINC01563andMALAT1are highly enriched in the nuclear fraction of GSCs. Together, this study identified a panel of uncharacterized GSC-specific lncRNAs. These findings set the stage for future in-depth studies to examine their role in GBM pathology and their potential as biomarkers and/or therapeutic targets in GBM.
Archaeal type IV pili stabilizeHaloferax volcaniibiofilms in flow
Authors: Odermatt Pascal D. , Nussbaum Phillip , Monnappa Sourabh , Talà Lorenzo , Li Zhengqun , Sivabalasarma Shamphavi , Albers Sonja-Verena , Persat Alex
Published: January 2023

Biofilms represent a prevalent lifestyle of unicellular organism that confers protection to external challenges. The mechanisms by which archaea form biofilms are however not entirely clear.H. volcaniiis an extremely halophilic euryarchaeon that commonly colonizes salt crust surfaces.H. volcaniiproduces long and thin appendages called type IV pili that are known to play a function in surface attachment and biofilm formation in archaea and bacteria. Here, we used biophysical experiments to identify critical function of type IV pili in the mechanical integrity ofH. volcaniibiofilms. Using interferometric scattering microscopy (iSCAT) to non-invasively visualize T4P in live cells, we find that piliation varies across mutants expressing single pilin isoforms. Using microfluidic experiments, we found that the adhesive strength of these mutants correlates with their extent of piliation. We found that in flow,H. volcaniiforms clonal biofilms that extend in three dimensions. Expression of PilA2, a single pilin isoform, is sufficient to maintain normal levels of piliation and form biofilms with a structure indistinguishable from WT. Furthermore, we found that fluid flow is a crucial determinant of biofilm integrity: in the absence of flow, biofilms lose cohesion and tend to disperse in a density-dependent manner. Overall, our results demonstrate that T4P-surface and possibly T4P-T4P interactions promote biofilm formation and integrity, and that flow is a crucial ingredient regulating archaeal biofilm formation.
A highly discriminatory RNA strand-specific assay to facilitate analysis of the role ofcis-acting elements in foot-and-mouth disease virus replication
Authors: Dobson Samuel J. , Ward Joseph C. , Herod Morgan R. , Rowlands David J. , Stonehouse Nicola J.
Published: January 2023

Foot-and-mouth-disease virus (FMDV), the etiological agent responsible for foot-and-mouth disease (FMD), is a member of the genusAphthoviruswithin thePicornavirusfamily. In common with all picornaviruses, replication of the single-stranded positive-sense RNA genome involves synthesis of a negative-sense complementary strand that serves as a template for the synthesis of multiple positive-sense progeny strands. We have previously employed FMDV replicons to examine viral RNA and protein elements essential to replication, however, the factors affecting differential strand production remain unknown. Replicon-based systems require transfection of high levels of RNA, which can overload sensitive techniques such as qPCR preventing discrimination of specific strands. Here, we describe a method in which replicating RNA is labelledin vivowith 5-ethynyl uridine. The modified base is then linked to a biotin tag using click chemistry, facilitating purification of newly synthesised viral genomes or anti-genomes from input RNA. This selected RNA can then be amplified by strand-specific qPCR, thus enabling investigation of the consequences of defined mutations on the relative synthesis of negative-sense intermediate and positive-strand progeny RNAs. We apply this new approach to investigate the consequence of mutation of viralcis-acting replication elements and provide direct evidence for their roles in negative-strand synthesis.