bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic architecture of leaf morphology revealed by integrated trait module in Catalpa bungei
Authors: Zhang Miaomiao , Liu Bingyang , Fei Yue , Yang Xiaowei , Zhao Linjiao , Shi Chaozhong , Zhang Yueying , Lu Nan , Wu Chuangye , Ma Wenjun , Wang Junhui
Published: February 2023

Leaves are crucial for maintaining plant growth and development via photosynthesis, and their function is simultaneously regulated by a suite of phenotypic traits. Although much is known about the genetic architecture of individual leaf traits, unraveling the genetic basis of complex leaf morphology remains a challenge. Based on the functional correlation and coordination of multi-traits, we divided 15 leaf morphological traits into three modules, comprising size (area, length, width, and perimeter), shape (leaf lobes, aspect ratio, circularity, rectangularity, and the relevant ratios), and color (red, green, and blue) for an ornamental tree species, Catalpa bungei. A total of 189 significant single-nucleotide polymorphisms were identified in the leaves of C. bungei: 35, 82, and 76 in the size, shape, and color modules, respectively. Four quantitative trait loci were common between the size and shape modules, which were closely related according to phenotype correlation, genetic mapping, and mRNA analysis. The color module was independent of them. Synergistic changes in the aspect ratio, leaf lobe, and circularity suggest that these traits could be the core indicators of the leaf shape module. The LAS and SRK genes, associated with leaf lobe and circularity, were found to function in plant defense mechanisms and the growth of leaves. The associations between the SRK and CRK2 genes and the leaf lobe and circularity traits were further verified by RT–qPCR. Our findings demonstrate the importance of integrating multi-trait modules to characterize leaf morphology and facilitate a holistic understanding of the genetic architecture of intraspecific leaf morphology diversity.
Big Data, Machine Learning and Contraceptive Use: A Scoping Review
Authors: Finnegan Amy , Subburaj Saisahana , Hunter Kelly , Parkash Priya , Shulman Elizabeth , Ramkalawan Janel , Huchko Megan J
Published: February 2023

The use of big data sources, like Twitter, and big data analytical techniques, like machine learning, have increased in popularity in almost every area of scientific inquiry. However, recent reviews have not focused on contraceptive use to prevent pregnancy, which is surprising considering that over one-third of unmet need for contraception in low- and middle-income countries is made up of women who have discontinued a method. This manuscript details the results of a scoping review of peer-reviewed literature at the intersection of big data and contraceptive use to prevent pregnancy. We developed the Metrics of Reliability and Quality (MARQ) to provide guidance to assess studies using big data to understand contraceptive use and beyond. We found 31 articles that matched our inclusion criteria. The oldest article was published in 1971, and 61.3% (N = 19) of articles were published after 2016. Many articles using big data sources applied traditional analytical methods rather than big data methods. The overall quality of articles on the MARQ rubric was high; however, many articles employing big data sources did not discuss specific limitations, such as population representativeness or bias, and articles using big data methods seldom demonstrated whether big data methods outperform traditional analytical methods.
Essential role for albumin in preserving liver cells from TNFα‐induced mitochondrial injury
Authors: Duran‐Güell Marta , Garrabou Glòria , Flores‐Costa Roger , Casulleras Mireia , López‐Vicario Cristina , Zhang Ingrid W. , Cantó‐Santos Judith , Contreras Bryan J. , Sánchez‐Rodríguez María B. , Romero‐Grimaldo Berta , Horrillo Raquel , Costa Montserrat , Arroyo Vicente , Clària Joan
Published: February 2023

Cytokine‐induced inflammation and mitochondrial oxidative stress are key drivers of liver tissue injury. Here, we describe experiments modeling hepatic inflammatory conditions in which plasma leakage leads to large amounts of albumin to reach the interstitium and parenchymal surfaces to explore whether this protein plays a role in preserving hepatocyte mitochondria against the damaging actions of the cytotoxic cytokine tumor necrosis factor alpha (TNFα). Hepatocytes and precision‐cut liver slices were cultured in the absence or presence of albumin in the cell media and then exposed to mitochondrial injury with the cytokine TNFα. The homeostatic role of albumin was also investigated in a mouse model of TNFα‐mediated liver injury induced by lipopolysaccharide and D‐galactosamine (LPS/D‐gal). Mitochondrial ultrastructure, oxygen consumption, ATP and reactive oxygen species (ROS) generation, fatty acid β‐oxidation (FAO), and metabolic fluxes were assessed by transmission electron microscopy (TEM), high‐resolution respirometry, luminescence‐fluorimetric‐colorimetric assays and NADH/FADH2 production from various substrates, respectively. TEM analysis revealed that in the absence of albumin, hepatocytes were more susceptible to the damaging actions of TNFα and showed more round‐shaped mitochondria with less intact cristae than hepatocytes cultured with albumin. In the presence of albumin in the cell media, hepatocytes also showed reduced mitochondrial ROS generation and FAO. The mitochondria protective actions of albumin against TNFα damage were associated with the restoration of a breakpoint between isocitrate and α‐ketoglutarate in the tricarboxylic acid cycle and the upregulation of the antioxidant activating transcription factor 3 (ATF3). The involvement of ATF3 and its downstream targets was confirmed in vivo in mice with LPS/D‐gal‐induced liver injury, which showed increased hepatic glutathione levels, indicating a reduction in oxidative stress after albumin administration. These findings reveal that the albumin molecule is required for the effective protection of liver cells from mitochondrial oxidative stress induced by TNFα. These findings emphasize the importance of maintaining the albumin levels in the interstitial fluid within the normal range to protect the tissues against inflammatory injury in patients with recurrent hypoalbuminemia.
A Novel Cell-based Luciferase Reporter Platform for the Development and Characterization of T-Cell Redirecting Therapies and Vaccine Development
Authors: Grailer Jamison , Cheng Zhijie Jey , Hartnett Jim , Slater Michael , Fan Frank , Cong Mei
Published: February 2023

T-cell immunotherapies are promising strategies to generate T-cell responses towards tumor-derived or pathogen-derived antigens. Adoptive transfer of T cells genetically modified to express antigen receptor transgenes has shown promise for the treatment of cancer. However, the development of T-cell redirecting therapies relies on the use of primary immune cells and is hampered by the lack of easy-to-use model systems and sensitive readouts to facilitate candidate screening and development. Particularly, testing T-cell receptor (TCR)-specific responses in primary T cells and immortalized T cells is confounded by the presence of endogenous TCR expression which results in mixed alpha/beta TCR pairings and compresses assay readouts. Herein, we describe the development of a novel cell-based TCR knockout (TCR-KO) reporter assay platform for the development and characterization of T-cell redirecting therapies. CRISPR/Cas9 was used to knockout the endogenous TCR chains in Jurkat cells stably expressing a human interleukin-2 promoter-driven luciferase reporter gene to measure TCR signaling. Reintroduction of a transgenic TCR into the TCR-KO reporter cells results in robust antigen-specific reporter activation compared with parental reporter cells. The further development of CD4/CD8 double-positive and double-negative versions enabled low-avidity and high-avidity TCR screening with or without major histocompatibility complex bias. Furthermore, stable TCR-expressing reporter cells generated from TCR-KO reporter cells exhibit sufficient sensitivity to probe in vitro T-cell immunogenicity of protein and nucleic acid-based vaccines. Therefore, our data demonstrated that TCR-KO reporter cells can be a useful tool for the discovery, characterization, and deployment of T-cell immunotherapy.
Histopathological Characteristics of Lacrimal Gland Prolapse
Authors: Huang Sonia , Juniat Valerie , James Craig , McNab Alan , Selva Dinesh
Published: February 2023

Purpose:

Lacrimal gland prolapse is an acquired clinical condition that can present as an upper eyelid mass. Patients may undergo lacrimal gland biopsy when there is diagnostic uncertainty. We aim to describe the histopathological features of this patient group.

Methods:

Retrospective case series involving 11 patients.

Results:

The mean age at presentation was 52.3 ± 16.2 years (range: 31–77 years) with 8 patients (72.3%) being female. The most common presenting symptom was a palpable mass (9; 81.8%) followed by dermatochalasis (4; 36.4%). Three cases (27.3%) were bilateral. Common imaging findings include lacrimal gland enlargement and visualization of the prolapse. All biopsies demonstrated features of mild chronic inflammation with preserved glandular structures. Ten patients (90.9%) underwent surgical intervention involving lacrimal gland pexy and 1 patient (9.1%) was elected for observation only. One patient required repeat surgery after 4 years due to recurrence of symptoms. At the last follow-up, all patients had stable disease or complete resolution of symptoms.

Conclusion:

We present a case series of patients diagnosed with lacrimal gland prolapse who underwent a biopsy during their workup. All biopsies demonstrated features of mild chronic inflammation (dacryoadenitis). All patients had stable disease or complete resolution of symptoms. This case series suggests that chronic inflammation is a common finding in patients with lacrimal gland prolapse but bears minimal clinical consequence.
Bilateral Congenital Nasolacrimal Duct Obstruction in Williams-Beuren Syndrome
Authors: Terrell Jesse A. , Mudie Lucy I. , Williams Katherine J. , Yen Michael T.
Published: February 2023

A 23-year-old patient with Williams-Beuren syndrome presented with ocular irritation and bilateral persistent tearing. Despite probing as an infant which showed bilateral nasolacrimal duct obstruction, dacryocystorhinostomy had been avoided due to the patient’s syndromic supravalvular stenosis and related anesthesia risk. As the known diminished production of elastin in Williams-Beuren syndrome causes an array of associated vascular diseases, this case report hypothesizes that the lacrimal duct becomes obstructed through a similar mechanism. This case presents the unique findings of bilateral congenital nasolacrimal duct stenosis in a Williams-Beuren syndrome patient.
Idiopathic Intracranial Hypertension in Female-to-Male Transgender Patients on Exogenous Testosterone Therapy
Authors: Gutkind Naomi E. , Tse David T. , Johnson Thomas E. , Tse Brian C.
Published: February 2023

Purpose:

To present four female-to-male (FTM) transgender patients on testosterone therapy diagnosed with idiopathic intracranial hypertension (IIH).

Methods:

The authors report 4 consecutive FTM transgender patients on exogenous testosterone diagnosed with IIH at a single institution.

Results:

Patient 1 presented with progressive blurred vision and a central scotoma 10 weeks after starting testosterone cypionate injections for hormonal gender transition. Bilateral grade 5 papilledema was present; the patient underwent bilateral optic nerve sheath fenestration with improved vision and resolution of edema. Patient 2 presented with transient vision loss, pulsatile tinnitus, and blurred vision 13 months after starting testosterone cypionate injections. The patient had grade 4 and 3 disc edema of the right and left eyes, respectively. Patient 3 presented with headaches and pulsatile tinnitus and was on testosterone injections at an unknown dose. The examination revealed grade 1 and 2 disc edema of the right and left eyes, respectively. Patient 4 presented with decreased vision, transient visual obscurations, and daily migraines while using topical testosterone gel every other day. Color vision was reduced, and lumbar puncture revealed elevated intracranial pressure. All patients had neuroimaging findings consistent with increased intracranial pressure.

Conclusions:

Testosterone therapy plays an essential role in FTM hormonal transitioning and may play a role in IIH. Patients undergoing testosterone therapy for gender transition should be informed of the possibility of developing IIH while on treatment, with obesity possibly increasing this risk. Comprehensive eye examinations should be considered in these patients before initiating hormone therapy.
Blood Concentrations of Volatile Organic Compounds Among US Workers From Various Trades
Authors: Zhang Kunqi , Lan Tuo , Bao Wei , Cui Qingbin , Thorne Peter S.
Published: February 2023

Objective

This study aimed to examine blood benzene, toluene, ethylbenzene, o-xylene, and m-/p-xylene (BTEX) concentrations and their trends contrasting construction workers with workers in other occupations from 1999 to 2014 in the United States. Methods: Using data from the National Health and Nutrition Examination Survey, quantile regressions were performed to investigate associations between occupation and blood BTEX concentrations. Results: We found that high-risk and construction occupations were associated with increased blood concentrations of toluene, o-xylene, and m-/p-xylene at the 50–90th percentiles (P50–90), and ethylbenzene at P70–90. Moreover, although blood concentrations of ethylbenzene, o-xylene, and m-/p-xylene trended down among all US workers, no decreasing trend was observed for benzene and toluene among construction workers. Conclusions: Future studies are warranted to address questions about specific tasks to better assess VOC exposure from various trades.
Shared Leadership for Total Worker Health in the Construction Industry
Authors: Schwatka Natalie V. , Johnson Stefanie , Schilz Matthew
Published: February 2023

Objective

The purpose of this study is to investigate the organizational, supervisor, team, and individual factors associated with employee and leader perceptions of shared Total Worker Health (TWH) transformational leadership in teams. Methods: We conducted a cross-sectional study with 14 teams across three construction companies. Results: Shared TWH transformational leadership in teams was associated with employees and leaders' perceptions of support from coworkers. Other factors were also associated it, but it differed by position. Conclusions: We found that leaders may be focused on the mechanics of sharing TWH transformational leadership responsibilities and workers may be more focused on their internal cognitive abilities and motivations. Our results suggest the potential ways of promoting shared TWH transformational leadership among construction teams.
How Work Pattern Transformation May Affect the Mental Health of Older Workers Faced With Unmet Health Care Needs During the Pandemic? A Comparative Investigation of Different Work Models
Authors: Yuan Bocong , Wang Muqing
Published: February 2023

Purpose

This study compares the relation between unmet health care needs and mental health of older people with different work patterns.

Methods

This study uses data of Survey of Health, Aging and Retirement in Europe Corona survey (n = 51,632 to 51,731).

Results

The unmet health care need results in depression/sadness during the pandemic (0.304, P < 0.01). Besides, such problem is more salient in workers than the nonemployed population (0.066, P < 0.01 for workers; 0.058, P < 0.01 for the nonemployed) and more outstanding in those working on site and with hybrid work model compared with the telecommuters (0.264, P < 0.01 for telecommuters; 0.378, P < 0.01 for on-site workers; 0.437, P < 0.01 for hybrid work model).

Conclusions

Policymakers should focus on mental health of older people especially for those fully or partially involved in on-site work, when common health care need can be crowded out for limited health care resources during the pandemic.
HIGH-MOLECULAR-WEIGHT HYALURONAN—A POTENTIAL ADJUVANT TO FLUID RESUSCITATION IN ABDOMINAL SEPSIS?
Authors: Barrueta Tenhunen Annelie , van der Heijden Jaap , Dogné Sophie , Flamion Bruno , Weigl Wojciech , Frithiof Robert , Skorup Paul , Larsson Anders , Larsson Anders , Tenhunen Jyrki
Published: February 2023

While fluid resuscitation is fundamental in the treatment of sepsis-induced tissue hypoperfusion, a sustained positive fluid balance is associated with excess mortality. Hyaluronan, an endogenous glycosaminoglycan with high affinity to water, has not been tested previously as adjuvant to fluid resuscitation in sepsis. In a prospective, parallel-grouped, blinded model of porcine peritonitis sepsis, we randomized animals to intervention with adjuvant hyaluronan (add-on to standard therapy, n = 8) or 0.9% saline (n = 8). After the onset of hemodynamic instability, the animals received an initial bolus of 0.1% hyaluronan (1 mg/kg/10 min) or placebo (0.9% saline) followed by a continuous infusion of 0.1% hyaluronan (1 mg/kg/h) or saline during the experiment. We hypothesized that the administration of hyaluronan would reduce the volume of fluid administered (aiming at stroke volume variation <13%) and/or attenuate the inflammatory reaction. Total volumes of intravenous fluids infused were 17.5 ± 11 versus 19.0 ± 7 mL/kg/h in intervention and control groups, respectively (P = 0.442). Plasma IL-6 increased to 2,450 (1,420–6,890) pg/mL and 3,690 (1,410–11,960) pg/mL (18 hours of resuscitation) in the intervention and control groups (nonsignificant). The intervention counteracted the increase in proportion of fragmented hyaluronan associated with peritonitis sepsis (mean peak elution fraction [18 hours of resuscitation] intervention group: 16.8 ± 0.9 versus control group: 17.9 ± 0.6 [P = 0.031]). In conclusion, hyaluronan did not reduce the volume needed for fluid resuscitation or decrease the inflammatory reaction, even though it counterbalanced the peritonitis-induced shift toward increased proportion of fragmented hyaluronan.
Universal Urogynecologic Consultation and Screening for Fecal Incontinence in Pregnant Women With a History of Obstetric Anal Sphincter Injury: A Cost-Effectiveness Analysis
Authors: Swallow Christina H. , Harvey Christina N. , Harmanli Oz , Shepherd Jonathan P.
Published: February 2023

Importance

Obstetric anal sphincter injuries (OASIS) predispose for the development of fecal incontinence (FI), but management of subsequent pregnancy after OASIS is controversial.

Objective

We aimed to determine if universal urogynecologic consultation (UUC) for pregnant women with prior OASIS is cost-effective.

Study Design

We performed a cost-effectiveness analysis of pregnant women with a history of OASIS modeling UUC compared with no referral (usual care). We modeled the route of delivery, peripartum complications, and subsequent treatment options for FI. Probabilities and utilities were obtained from published literature. Costs using a third-party payer perspective were gathered from the Medicare physician fee schedule reimbursement data or published literature converted to 2019 U.S. dollars. Cost-effectiveness was determined using incremental cost-effectiveness ratios).

Results

Our model demonstrated that UUC for pregnant patients with prior OASIS was cost-effective. Compared with usual care, the incremental cost-effectiveness ratio for this strategy was $19,858.32 per quality-adjusted life-year, below the willingness to pay a threshold of $50,000/quality-adjusted life-year. Universal urogynecologic consultation reduced the ultimate rate of FI from 25.33% to 22.67% and reduced patients living with untreated FI from 17.36% to 1.49%. Universal urogynecologic consultation increased the use of physical therapy by 14.14%, whereas rates of sacral neuromodulation and sphincteroplasty increased by only 2.48% and 0.58%, respectively. Universal urogynecologic consultation reduced the rate of vaginal delivery from 97.26% to 72.42%, which in turn led to a 1.15% increase in peripartum maternal complications.

Conclusions

Universal urogynecologic consultation in women with a history of OASIS is a cost-effective strategy that decreases the overall incidence of FI, increases treatment utilization for FI, and only marginally increases the risk of maternal morbidity.
Perioperative Outcomes of Colpocleisis at a Single Institution: A Retrospective Cohort Study
Authors: Simms Lauren , Maheshwari Deepali , Harmanli Oz , Rastegar Vida , Diaz Naomi , Jones Keisha
Published: February 2023

Importance

There is limited literature reporting perioperative outcomes among colpocleisis types.

Objectives

This study aimed to describe perioperative outcomes after colpocleisis at a single institution.

Study Design

Patients who underwent colpocleisis at our academic medical center between August 2009 and January 2019 were included. A retrospective chart review was performed. Descriptive and comparative statistics were generated.

Results

A total of 367 of 409 eligible cases were included. Median follow-up was 44 weeks. There were no major complications or mortalities. Le Fort and posthysterectomy colpocleises were faster than transvaginal hysterectomy (TVH) with colpocleisis (95 and 98 minutes, respectively, vs 123 minutes; P = 0.00) with decreased estimated blood loss (100 and 100 mL, respectively, vs 200 mL; P = 0.000). Urinary tract infection and postoperative incomplete bladder emptying occurred in 22.6% and 13.4% of all patients, respectively, with no difference among the colpocleisis groups (P = 0.83 and P = 0.90). Patients who underwent concomitant sling were not at increased risk of postoperative incomplete bladder emptying (14.7% for Le Fort and 17.2% for total colpocleisis). Prolapse recurred after 0 Le Fort (0%), 6 posthysterectomy (3.7%), and 0 TVH with colpocleisis procedures (0%) (P = 0.02).

Conclusions

Colpocleisis is a safe procedure with a relatively low complication rate. Le Fort, posthysterectomy, and TVH with colpocleisis have similarly favorable safety profiles and very low overall recurrence rates. Concomitant TVH at the time of colpocleisis is associated with increased operative time and increased blood loss. Concomitant sling procedure at the time of colpocleisis does not increase the risk of short-term incomplete bladder emptying.
The coat protein of the ilarvirus prunus necrotic ringspot virus mediates long-distance movement
Authors: He Chengyong , Xing Fei , Zhao Xiaoli , Li Shifang , Zhan Binhui , Liu Zhen , Xu Tengfei , Gao Dehang , Dong Zhenfei , Wang Hongqing , Zhang Zhixiang
Published: February 2023

The coat protein (CP) of plant viruses generally has multiple functions involving infection, replication, movement and pathogenicity. Functions of the CP of prunus necrotic ringspot virus (PNRSV), the causal agent of several threatening diseases of Prunus fruit trees, are poorly studied. Previously, we identified a novel virus in apple, apple necrotic mosaic virus (ApNMV), which is phylogenetically related to PNRSV and probably associated with apple mosaic disease in China. Full-length cDNA clones of PNRSV and ApNMV were constructed, and both are infectious in cucumber (Cucumis sativus L.), an experimental host. PNRSV exhibited higher systemic infection efficiency with more severe symptoms than ApNMV. Reassortment analysis of genomic RNA segments 1–3 found that RNA3 of PNRSV could enhance the long-distance movement of an ApNMV chimaera in cucumber, indicating the association of RNA3 of PNRSV with viral long-distance movement. Deletion mutagenesis of the PNRSV CP showed that the basic motif from amino acids 38 to 47 was crucial for the CP to maintain the systemic movement of PNRSV. Moreover, we found that arginine residues 41, 43 and 47 codetermine viral long-distance movement. The findings demonstrate that the CP of PNRSV is required for long-distance movement in cucumber, which expands the functions of ilarvirus CPs in systemic infection. For the first time, we identified involvement of Ilarvirus CP protein during long-distance movement.
Hacking Acute Care: A Qualitative Study on the Healthcare Impacts of Ransomware Attacks Against Hospitals
Authors: van Boven Liselotte S. , Kusters Renske W.J. , Tin Derrick , van Osch Frits H. M. , De Cauwer Harald , Ketelings Linsay , Rao Madhura , Dameff Christian , Barten Dennis G.
Published: February 2023

Background and objectives

Cyberattacks against healthcare institutions are an increasing threat and have the potential to impair health outcomes. Current research is limited and focuses mainly on the technical consequences, whereas little is known about the healthcare staff experiences and the impact on emergency care, both during the incident and in the recovery phase. This study aims to explore the impact of a sample of large ransomware attacks against hospitals between 2017 and 2022 on acute care delivery and patient care during the recovery phase.

Methods

This interview-based qualitative study assessed the experiences of emergency healthcare professionals and Information and Communication Technology (ICT) staff and investigated the challenges faced when struck by a major hospital ransomware attack. The semi-structured interview guideline was based on current literature and cybersecurity expert consultation. Transcripts were anonymized and information tracing back to participants and/or their organizations was removed for privacy purposes.

Results

Nine participants were interviewed, including emergency healthcare providers and ICT-focused staff. Five themes were constructed from the data: impact and challenges regarding patient care continuity, challenges during the recovery process, personal impact on healthcare staff, preparedness, and lessons identified and future recommendations.

Conclusions

According to the participants of this qualitative study, ransomware attacks have a significant impact on emergency department (ED) workflow, acute patient care and the personal wellbeing of healthcare providers. Preparedness for such incidents is often limited and many challenges are encountered during the acute and recovery phase of the attack. Proactive preparedness efforts are essential to improve contingency planning and to develop response strategies for hospital ransomware attacks.
Chromosome-level genome assembly of tree sparrow reveals a burst of new genes driven by segmental duplications
Authors: Wang Shengnan , Zhang Yingmei , Shen Yue , Lin Zhaocun , Miao Yuquan , Ji Yanzhu , Song Gang
Published: February 2023

The creation of new genes is a major force of evolution. Despite as an important mechanism that generated new genes, segmental duplication (SD) has yet to be accurately identified and fully characterized in birds because the repetitive complexity leads to misassignment and misassembly of sequence. In addition, SD may lead to new gene copies, which makes it possible to test the “out of testis” hypothesis which suggests genes are frequently born with testis-specific expression. Using a high-quality chromosome-level assembly, we performed a systematic analysis and presented a comprehensive landscape of SDs in tree sparrow (Passer montanus). We detected co-localization of newly expanded genes and long terminal repeat retrotransposons (LTR-RTs), both of which are derived from SDs and enriched in microchromosomes. The newly expanded genes are mostly found in eight families includingC2H2ZNF, OR, PIM, PAK, MROH, HYDIN, HSFandITPRIPL. The large majority of new members of these eight families have evolved to pseudogenes, whereas there still some new copies preserved transcriptional activity. Among the transcriptionally active new members, new genes from different families with diverse structures and functions shared a similar testis-biased expression pattern, which is consistent with the “out of testis” hypothesis. Through a case analysis of the high-quality genome assembly of tree sparrow, we reveal that the SDs contribute to the formation of new genes. Our study provides a comprehensive understanding of the emergence, expression and fate of duplicated genes and how the SDs might participate in these processes and shape genome evolution.
Multi-omics and Pharmacological Characterization of Patient-derived Glioma Cell Lines
Authors: Wu Min , Yuan Ran , Ji Nan , Lu Ting , Wang Tingting , Zhang Junxia , Li Mengyuan , Cao Penghui , Zhao Jiarui , Li Guanzhang , Li Jianyu , Li Yu , Tang Yujie , Gao Zhengliang , Wang Xiuxing , Wu Anhua , Cheng Wen , Ge Ming , Cui Gang , You Yongping , Zhang Wei , Wang Qianghu , Chen Jian
Published: February 2023

Glioblastoma (GBM) is the most common brain tumor and is currently incurable. Primary GBM cultures are widely used tools for screening potentially therapeutic drugs; however, there is a lack of genomic and pharmacological characterization of these primary GBM cultures. Here, we collected 52 patient-derived glioma cell (PDGC) lines and characterized them through whole- genome sequencing (WGS), RNA-seq, and drug response screening. We identified three molecular subtypes among PDGCs: mesenchymal (MES), proneural (PN), and oxidative phosphorylation (OXPHOS). Upon profiling the responses of PDGCs to 214 drugs, we found that the PN subtype PDGCs were sensitive to tyrosine kinase inhibitors, whereas the OXPHOS subtype PDGCs were sensitive to histone deacetylase inhibitors, oxidative phosphorylation inhibitors, and HMG-CoA reductase inhibitors. PN and OXPHOS subtype PDGCs stably formed tumorsin vivoupon intracranial transplantation into immunodeficient mice, while most MES subtype PDGCs were incapable of tumorigenesisin vivo. In addition, profiling and follow-up investigations showed that the serum-free culture system used for PDGCs enriched and propagated rareMYC/MYCN- amplified glioma cells. Our study provides a resource for understanding primary glioma cell cultures and aiding clinical translation.

Significance

Our study provides a resource for patient-derived glioma cell lines (PDGCs) on transcriptome, genome, drug response, and tumorigenic abilities. PDGCs are categorized into PN, MES, and OXPHOS subtypes, with MES-subtype PDGCs incapable of tumorigenesisin vivo. Notably, the serum-free culture system for PDGCs enriches glioma cells withMYC/MYCNamplification.
Next-generation CRISPR gene-drive systems using Cas12a nuclease
Authors: Juste Sara Sanz , Okamoto Emily M. , Feng Xuechun , Del Amo Victor López
Published: February 2023

One method for reducing the impact of vector-borne diseases is through the use of CRISPR-based gene drives, which manipulate insect populations due to their ability to rapidly propagate desired genetic traits into a target population. However, all current gene drives employ a Cas9 nuclease that is constitutively active, impeding our control over their propagation abilities and limiting the generation of novel gene drive arrangements. Yet, other nucleases such as the temperature-sensitive Cas12a have not been explored for gene drive designs. To address this, we herein present a proof-of-concept gene-drive system driven by Cas12a that can be regulated via temperature modulation. Furthermore, we combined Cas9 and Cas12a to build double gene drives capable of simultaneously spreading two independent engineered alleles. The development of Cas12a-mediated gene drives provides an innovative option for designing next-generation vector control strategies to combat disease vectors and agricultural pests.
The Baptism of an Indian Juggler: Event and Narrative in the Swedish Press, 1827–1852
Authors: Carlesson Magalhães Jens , Jansson Fredrik
Published: February 2023

In 1827, an Indian juggler named Mooty Madua Samme converted to Christianity in Stockholm, Sweden. This historical event got much attention in the press at the time – as did his succeeding marriage to a Swedish woman named Erica – and was celebrated as a victory for the Evangelical Lutheran faith. Later, in the 1840s, a narrative depicting the event spread via a travelogue by Xavier Marmier, which was translated and mediated through the Swedish press, and reacted to by Samme's priest; in the 1850s, Samme's name surfaced again – now in context of the contemporary freedom of religion debates in Sweden. In this article, we explore Samme's baptism (and interrelatedly, his marriage) by looking at newspaper mediations of the event and the related narratives. Seen from a microhistorical perspective, we show how Samme's conversion and religious otherness was utilised in contemporary religious and political discussions, and we argue that the event and narratives surrounding the baptism can augment our understanding of the Swedish nineteenth century religio‐cultural landscape in which he was situated.
Experimentation as infrastructure: Enacting transitions differently through diverse economy‐environment assemblages in Aotearoa New Zealand
Authors: Dowell Angus , Lewis Nick , Jones Ryan
Published: February 2023

Radically new economic arrangements are needed for just and sustainable transitions to a more environmentally and ecologically resilient world. Yet little progress is being made to imagine the new economy‐environment relations around which resources, actors, and ethics might be configured to enact the novel economic forms needed. This article uses a Social Studies of Economisation and Marketisation (SSEM) approach to examine a suite of differently scaled and structured environmentally focused economic development initiatives in New Zealand. We explore how the initiatives have assembled diverse actors and investment projects into experimental economy‐environment relations. Our account highlights experimentation as a pivotal mode of economisation, and we argue that the initiatives studied by us expose a new experimentation‐led agenda for transitioning to more environmentally and economically just futures. Working with the idea of experimentation in an SSEM framework, we also argue that the diverse initiatives are creating an experimentation infrastructure that provides a more generative platform for novel economy‐environment relations than top–down models of change such as transition pathways. The article opens up a critical politics of environmental economy that focuses attention on emergence, agency, and practice and allows us to reimagine processes of transitioning.
Petroleum Generation Kinetics and Geological Implications for Jurassic Hydrocarbon Source Rocks, Hongqi Depression, Hailar Basin, Northeast China
Authors: XIE Mingxian , MA Feng , CHEN Guangpo , LIU Chang , XIAO Rong , SU Yuping , ZHANG Chengjun
Published: February 2023

A sample from the Jurassic Tamulangou Fm. and two comparison samples from the Cretaceous Fm. were used to document the hydrocarbon generation kinetics and phase behaviors at two heating rates using the confined gold tube system. The results show that the different heating rates affect the reaction rates, paths and levels of organic matter evolution. The average activation energy and dominant frequency activation energy of liquid hydrocarbon are significantly lower than those of gaseous. Moreover, igneous intrusion had a positive effect on the blooming, enrichment and preservation of organic matter, promoting a Ro increase of 0.09%–1.07% in the Jurassic Tamulangou Fm. Two models were used to simulate the normal and abnormal evolution caused by thermal events combined hydrocarbon generation kinetic parameters. Thermal simulation analysis shows that oil generation was initially slow and then increased rapidly until a burial depth of 1500 m was reached at ~128 Ma. The largest hydrocarbon expulsion began at ~120 Ma, corresponding to a burial depth of 2450 m. The maximum cumulative yield is 510 mg/g TOC, and it is still in the peak period of hydrocarbon generation, which demonstrates a favorable potential for hydrocarbon exploration.
CCL26 in primary biliary cholangitis – Is it a novel disease mediator?
Authors: Sun Xiaochuan , Cao Yihan , Wang Li , Chen Hua , Zhang Fengchun
Published: February 2023

Aim

To verify the role of CX3C chemokine ligand 1 ‐ CX3C chemokine receptor 1 (CX3CL1‐CX3CR1) pathway in the pathogenesis of primary biliary cholangitis (PBC). To explore whether CCL26, a novel functional ligand to CX3CR1, participates in the immunological mechanism of PBC.

Methods

Fifty‐nine PBC patients and 54 healthy controls were recruited. Enzyme‐linked immunosorbent assay and flow cytometry were used to measure CX3CL1 and CCL26 concentrations in plasma and CX3CR1 expression on peripheral lymphocytes, respectively. Chemotactic effects of CX3CL1 and CCL26 toward lymphocytes were detected by Transwell cell migration assays. CX3CL1 and CCL26 expressions in liver were assessed by immunohistochemical staining. Effects of CX3CL1 and CCL26 on stimulating cytokine production from lymphocytes were evaluated using intracellular flow cytometry.

Results

Significantly elevated CX3CL1 and CCL26 plasma concentration and CX3CR1 expression on CD4+ and CD8+ T cells were noted in PBC patients. CX3CL1 exhibited chemotactic activity toward CD8+ T, natural killer (NK) and NKT cells in a dose‐dependent manner while such chemotactic effects were not detected for CCL26. In PBC patients, CX3CL1 and CCL26 were both increasingly expressed in biliary tracts and a concentration gradient of CCL26 in hepatocytes around portal areas was observed. Immobilized CX3CL1 could enhance interferon‐γ production from T and NK cells while such effect was not exhibited by soluble CX3CL1 or CCL26.

Conclusions

CCL26 expression is significantly elevated in plasma and biliary duct of PBC patients, yet does not appear to attract CX3CR1‐expressing immune cells. CX3CL1‐CX3CR1 pathway promotes the infiltration of T, NK and NKT cells into bile ducts and forms a positive feedback loop with T‐helper 1 type cytokines in PBC.
Conditional Mandates on Management Earnings Forecasts: The Impact on the Cost of Debt
Authors: Wang Kun Tracy , Zhu Nathan Zhenghang
Published: February 2023

Exploiting a unique conditional disclosure mandate on management earnings forecasts (MEFs) in China, we examine the differential effects of voluntary and mandatory MEFs on the cost of debt. We find that firms providing voluntary MEFs have lower cost of debt than do mandatory forecasters and nonforecasters. The results of the channel analyses reveal that voluntary forecasters have greater commitment to voluntary MEFs in future periods than do mandatory forecasters and nonforecasters, and the precision, accuracy, and timeliness of MEFs are higher for voluntary forecasters than for mandatory forecasters. Additional analyses show that the differential effects of voluntary and mandatory MEFs on cost of debt are stronger for voluntary forecasters operating in opaque information environments, issuing high‐quality and confirming forecasts, controlled by private shareholders, and operating in highly competitive product markets. Overall, our results indicate that, compared with mandatory MEFs, voluntary MEFs are more informative for credit investors, particularly for firms facing greater information risk and operating uncertainty.
Ambulatory follow‐up among publicly insured children discharged from the emergency department
Authors: Ramgopal Sriram , Rodean Jonathan , Alpern Elizabeth R. , Hall Matt , Chaudhari Pradip P. , Marin Jennifer R. , Shah Samir S. , Freedman Stephen B. , Eltorki Mohamed , Badaki‐Makun Oluwakemi , Shapiro Daniel J. , Rhine Tara , Morse Rustin B. , Neuman Mark I.
Published: February 2023

Background

While children discharged from the emergency department (ED) are frequently advised to follow up with ambulatory care providers, the extent to which this occurs is unknown. We sought to characterize the proportion of publicly insured children who have an ambulatory visit following ED discharge, identify factors associated with ambulatory follow‐up, and evaluate the association of ambulatory follow‐up with subsequent hospital‐based health care utilization.

Methods

We performed a cross‐sectional study of pediatric (<18 years) encounters during 2019 included in the IBM Watson Medicaid MarketScan claims database from seven U.S. states. Our primary outcome was an ambulatory follow‐up visit within 7 days of ED discharge. Secondary outcomes were 7‐day ED return visits and hospitalizations. Logistic regression and Cox proportional hazards were used for multivariable modeling.

Results

We included 1,408,406 index ED encounters (median age 5 years, IQR 2–10 years), for which a 7‐day ambulatory visit occurred in 280,602 (19.9%). Conditions with the highest proportion of 7‐day ambulatory follow‐up included seizures (36.4%); allergic, immunologic, and rheumatologic diseases (24.6%); other gastrointestinal diseases (24.5%); and fever (24.1%). Ambulatory follow‐up was associated with younger age, Hispanic ethnicity, weekend ED discharge, ambulatory encounters prior to the ED visit, and diagnostic testing performed during the ED encounter. Ambulatory follow‐up was inversely associated with Black race and ambulatory care–sensitive or complex chronic conditions. In Cox models, ambulatory follow‐up was associated with a higher hazard ratio (HR) of subsequent ED return (HR range 1.32–1.65) visit and hospitalization (HR range 3.10–4.03).

Conclusions

One‐fifth of children discharged from the ED have an ambulatory visit within 7 days, which varied by patient characteristics and diagnoses. Children with ambulatory follow‐up have a greater subsequent health care utilization, including subsequent ED visit and/or hospitalization. These findings identify the need to further research the role and costs associated with routine post‐ED visit follow‐up.
Early postnatal weight loss does not affect the 2‐year neurodevelopment in preterm infants of less than 32 weeks
Authors: Correani Alessio , Biagetti Chiara , Burattini Ilaria , Bellagamba Maria Paola , D'Ascenzo Rita , Ferretti Enrica , Peretti Anna , Monachesi Chiara , Simonato Manuela , Carnielli Virgilio
Published: February 2023

Aim

It is still unclear if the magnitude of early postnatal weight loss (PWL) could be associated with neurodevelopmental outcomes in preterm infants. We studied the association between PWL and neurodevelopment at 2‐year corrected age in preterm infants.

Methods

We retrospectively reviewed data of preterm infants with a gestational age between 24 + 0 and 31 + 6 weeks/days, admitted at the G.Salesi Children's Hospital, Ancona, Italy, between 1 January 2006 and 31 December 2019. Infants with PWL greater than or equal to 10% (PWL ≥ 10%) were compared with those with PWL of less than 10% (PWL < 10%). A matched cohort analysis was also performed using gestational age and birth weight as matching variables.

Results

We analysed 812 infants: 471 (58%) PWL ≥ 10% and 341 (42%) PWL < 10%. A subgroup of 247 PWL ≥ 10% was closely match‐paired with 247 PWL < 10% infants. There were no differences in amino acid and energy intakes from birth to day 14 of life and from birth to 36 weeks. Although at 36 weeks, body weight and total length were lower in PWL ≥ 10% than PWL < 10%, anthropometry and neurodevelopment at 2 years were similar between groups.

Conclusion

Given similar amino acid and energy intakes on PWL ≥ 10% and PWL < 10% preterm infants of less than 32 + 0 weeks/days, PWL does not affect 2‐year neurodevelopment.
The development of sleep‐like posture expression with age in female Holstein calves
Authors: Fukasawa Michiru
Published: February 2023

Sleep plays an important role in cattle production and welfare. Therefore, this study aimed to investigate the development of sleep‐like posture (SLP) expression in dairy calves from birth to the first calving as an indicator of their sleep behavior. Fifteen female Holstein calves were subjected. Daily SLP was measured eight times (0.5, 1, 2, 4, 8, 12, and 18 months and 23 months or 1 month before the first calving) using an accelerometer. Calves were kept in individual pens until weaning at 2.5 months old and then kept in the group. The daily SLP time decreased rapidly in early life; however, the rate of decrease gradually slowed and eventually reached a stable level of approximately 60 min/day after 12 months old. The daily SLP bout frequency showed the same change as the SLP time. In contrast, the averaged SLP bout duration slowly decreased with age. Longer daily SLP time during early life in female Holstein calves might be related to brain development. The individual expression of daily SLP time differs before and after weaning. Some external and/or internal factors associated with weaning may be involved SLP expression.
COVID‐19 vaccine attitudes and facilitators among people in Australia who inject drugs
Authors: Price Olivia , Maher Lisa , Dietze Paul M. , Bruno Raimondo , Crawford Sione , Sutherland Rachel , Salom Caroline , Dore Gregory J. , Peacock Amy
Published: February 2023

Introduction

We aimed to describe COVID‐19 vaccination attitudes and identify potential facilitators for vaccine uptake among people who inject drugs.

Methods

People who inject drugs were recruited from all eight Australian capital cities (N = 884; 65% male, mean age 44 years) and interviewed face‐to‐face or via telephone in June–July 2021. COVID‐19 and broader vaccination attitudes were used to model latent classes. Correlates of class membership were assessed through multinomial logistic regression. Probability of endorsing potential vaccination facilitators were reported by class.

Results

Three classes of participants were identified: ‘vaccine acceptant' (39%), ‘vaccine hesitant' (34%) and ‘vaccine resistant' (27%). Those in the hesitant and resistant groups were younger, more likely to be unstably housed and less likely to have received the current season influenza vaccine than the acceptant group. In addition, hesitant participants were less likely to report a chronic medical condition than acceptant participants. Compared to vaccine acceptant and hesitant participants, vaccine‐resistant participants were more likely to predominantly inject methamphetamine and to inject drugs more frequently in the past month. Both vaccine‐hesitant and resistant participants endorsed financial incentives for vaccination and hesitant participants also endorsed facilitators related to vaccine trust.

Discussion and Conclusion

People who inject drugs who are unstably housed or predominantly inject methamphetamine are subgroups that require targeted interventions to increase COVID‐19 vaccination uptake. Vaccine‐hesitant people may benefit from interventions that build trust in vaccine safety and utility. Financial incentives may improve vaccine uptake among both hesitant and resistant people.
New Multilateral Development Banks and Green Lending: Approaching Scalar Complexities in the Global South
Authors: Güngen Ali Rıza
Published: February 2023

Newly established multilateral development banks promote green finance and support a green transition in the global South. This article examines the new multilateral development banks using a dynamic view and documents the projects and lending preferences of New Development Bank (NDB) in Brazil and Asian Infrastructure Investment Bank (AIIB) in Turkey. While AIIB and NDB have made it easier for global South actors to access infrastructural investment funding and are committed to expanding green lending, their commitment rests on the use of country systems and national financial intermediaries. This results in extending loans for projects with significant risk and ignoring the broader connections of the projects to the environmentally hazardous strategies of capital accumulation. Despite their strong green discourse, their design and the way their mandates have been interpreted render new multilateral development banks prone to business as usual.
Vessel images of gallbladder polypoid lesions on detective flow imaging endoscopic ultrasonography
Authors: Miwa Haruo , Sugimori Kazuya , Maeda Shin
Published: February 2023

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