bluuebunny/crossref_metadata_2025 huggingface dataset:
The Snapdragon Genomes Reveal the Evolutionary Dynamics of the S-Locus Supergene
Authors: Zhu Sihui , Zhang Yu’e , Copsy Lucy , Han Qianqian , Zheng Dongfeng , Coen Enrico , Xue Yongbiao
Published: April 2023

The genus Antirrhinum has been used as a model to study self-incompatibility extensively. The multi-allelic S-locus, carrying a pistil S-RNase and dozens of S-locus F-box (SLF) genes, underlies the genetic control of self-incompatibility (SI) in Antirrhinum hispanicum. However, there have been limited studies on the genomic organization of the S-locus supergene due to a lack of high-quality genomic data. Here, we present the chromosome-level reference and haplotype-resolved genome assemblies of a self-incompatible A. hispanicum line, AhS7S8. For the first time, 2 complete A. hispanicum S-haplotypes spanning ∼1.2 Mb and containing a total of 32 SLFs were reconstructed, whereas most of the SLFs derived from retroelement-mediated proximal or tandem duplication ∼122 Mya. Back then, the S-RNase gene and incipient SLFs came into linkage to form the pro-type of type-1 S-locus in the common ancestor of eudicots. Furthermore, we detected a pleiotropic cis-transcription factor (TF) associated with regulating the expression of SLFs, and two miRNAs may control the expression of this TF. Interspecific S-locus and intraspecific S-haplotype comparisons revealed the dynamic nature and polymorphism of the S-locus supergene mediated by continuous gene duplication, segmental translocation or loss, and TE-mediated transposition events. Our data provide an excellent resource for future research on the evolutionary studies of the S-RNase-based self-incompatibility system.
Quantitative haplotype-resolved analysis of mitochondrial DNA heteroplasmy in Human single oocytes, blastoids, and pluripotent stem cells
Authors: Bi Chongwei , Wang Lin , Fan Yong , Yuan Baolei , Alsolami Samhan , Zhang Yingzi , Zhang Pu-Yao , Huang Yanyi , Yu Yang , Izpisua Belmonte Juan Carlos , Li Mo
Published: April 2023

Maternal mitochondria are the sole source of mtDNA for every cell of the offspring. Heteroplasmic mtDNA mutations inherited from the oocyte are a common cause of metabolic diseases and associated with late-onset diseases. However, the origin and dynamics of mtDNA heteroplasmy remain unclear. We used our individual Mitochondrial Genome sequencing (iMiGseq) technology to study mtDNA heterogeneity, quantitate single nucleotide variants (SNVs) and large structural variants (SVs), track heteroplasmy dynamics, and analyze genetic linkage between variants at the individual mtDNA molecule level in single oocytes and human blastoids. Our study presented the first single-mtDNA analysis of the comprehensive heteroplasmy landscape in single human oocytes. Unappreciated levels of rare heteroplasmic variants well below the detection limit of conventional methods were identified in healthy human oocytes, of which many are reported to be deleterious and associated with mitochondrial disease and cancer. Quantitative genetic linkage analysis revealed dramatic shifts of variant frequency and clonal expansions of large SVs during oogenesis in single-donor oocytes. iMiGseq of a single human blastoid suggested stable heteroplasmy levels during early lineage differentiation of naïve pluripotent stem cells. Therefore, our data provided new insights of mtDNA genetics and laid a foundation for understanding mtDNA heteroplasmy at early stages of life.
Defining the fine structure of promoter activity on a genome-wide scale with CISSECTOR
Authors: FitzPatrick Vincent D , Leemans Christ , van Arensbergen Joris , van Steensel Bas , Bussemaker Harmen J
Published: April 2023

Classic promoter mutagenesis strategies can be used to study how proximal promoter regions regulate the expression of particular genes of interest. This is a laborious process, in which the smallest sub-region of the promoter still capable of recapitulating expression in an ectopic setting is first identified, followed by targeted mutation of putative transcription factor binding sites. Massively parallel reporter assays such as survey of regulatory elements (SuRE) provide an alternative way to study millions of promoter fragments in parallel. Here we show how a generalized linear model (GLM) can be used to transform genome-scale SuRE data into a high-resolution genomic track that quantifies the contribution of local sequence to promoter activity. This coefficient track helps identify regulatory elements and can be used to predict promoter activity of any sub-region in the genome. It thus allows in silico dissection of any promoter in the human genome to be performed. We developed a web application, available at cissector.nki.nl, that lets researchers easily perform this analysis as a starting point for their research into any promoter of interest.
Chromosome-level, nanopore-only genome and allele-specific DNA methylation of Pallas's cat, Otocolobus manul
Authors: Flack Nicole , Drown Melissa , Walls Carrie , Pratte Jay , McLain Adam , Faulk Christopher
Published: April 2023

Pallas's cat, or the manul cat (Otocolobus manul), is a small felid native to the grasslands and steppes of central Asia. Population strongholds in Mongolia and China face growing challenges from climate change, habitat fragmentation, poaching, and other sources. These threats, combined with O. manul’s zoo collection popularity and value in evolutionary biology, necessitate improvement of species genomic resources. We used standalone nanopore sequencing to assemble a 2.5 Gb, 61-contig nuclear assembly and 17097 bp mitogenome for O. manul. The primary nuclear assembly had 56× sequencing coverage, a contig N50 of 118 Mb, and a 94.7% BUSCO completeness score for Carnivora-specific genes. High genome collinearity within Felidae permitted alignment-based scaffolding onto the fishing cat (Prionailurus viverrinus) reference genome. Manul contigs spanned all 19 felid chromosomes with an inferred total gap length of less than 400 kilobases. Modified basecalling and variant phasing produced an alternate pseudohaplotype assembly and allele-specific DNA methylation calls; 61 differentially methylated regions were identified between haplotypes. Nearest features included classical imprinted genes, non-coding RNAs, and putative novel imprinted loci. The assembled mitogenome successfully resolved existing discordance between Felinae nuclear and mtDNA phylogenies. All assembly drafts were generated from 158 Gb of sequence using seven minION flow cells.
DisseminatedTalaromyces marneffeiInfection With STAT3-Hyper-IgE Syndrome: A Case Series and Literature Review
Authors: Li Zhengtu , Yang Jinglu , Qiu Ye , Yang Feng , Tang Mengxin , Li Shaoqiang , Zhan Yangqing , Li Yongming , Tang Sufang , Jing Cheng , Ye Feng
Published: April 2023

Background

Little is known about the clinical characteristics of talaromycosis with hyper–immunoglobulin E syndrome (HIES).

Methods

We conducted a multicenter retrospective study, which included 7 hospitals from 2016 to 2022. Five consecutive cases of human immunodeficiency virus (HIV)–negative patients with systemic Talaromyces marneffei infections due to STAT3-HIES were identified. A systematic literature review of original articles published in English identified an additional 7 cases. Clinical characteristics and laboratory parameters were collected.

Results

Forty-two percent (5/12) of patients were young adults. The main symptoms of 10 patients were similar: fever (75%), cough (75%) and dyspnea (33%), but two patients mainly had gastrointestinal symptoms. Most patients had a history of infections since infancy. T marneffei was cultured from the bronchoalveolar lavage fluid (50%) and 25% of patients were next-generation sequencing positive. Eight patients had significantly elevated serum immunoglobulin E, increased B cells and decreased natural killer cells. There were ten different STAT3 mutations, three of which were reported for the first time in this study. Chest computed tomography examinations showed multiple exudations with cavities in the lungs. Voriconazole combined with thymosin was effective. Despite given antifungal agents, most had poor outcomes and the case fatality rate was as high as 25%.

Conclusions

STAT3-HIES is most likely a susceptibility factor for T marneffei infections among HIV-negative patients, which has a high case fatality rate. Increased awareness among clinicians is necessary to help in early diagnosis.
Ministerial Advisers as Power Resources: Exploring Expansion, Stability and Contraction in Westminster Ministers’ Offices
Authors: Pickering Heath , Craft Jonathan , Brans Marleen
Published: April 2023

In this article, we argue that the entourage of ministerial advisers available to prime ministers and other ministers is an institutional power resource that can serve as a useful indicator to measure the changing nature of the political executive. Two novel contributions are made utilising four new datasets on ministerial advisers coupled with a comparative analysis of 21 governments in Australia, Britain, Canada and New Zealand, in varying dates between 1997 and 2020. First, by using ministerial advisers as a proxy indicator, we chart how the offices of executive politicians can either expand, remain stable or contract. As a corrective to the general long-term narrative that ministers’ offices continually expand, our evidence shows this expansion has in some cases been interrupted and more generally manifests in different patterns from one government to the next. Second, we interrogate these patterns against the background of four typical assumptions from the party family, government tenure, parliamentary control and leadership stability literature. The new datasets, typology and analysis provide fresh comparative insights to advance our understanding about the evolving nature of the political executive in the four classic Westminster family countries.
Solutions to agricultural green water scarcity under climate change
Authors: He Liyin , Rosa Lorenzo
Published: April 2023

Rain-fed agricultural systems, which solely depend on green water (i.e. soil moisture from rainfall), sustain ∼60% of global food production and are particularly vulnerable to vagaries in temperature and precipitation patterns, which are intensifying due to climate change. Here, using projections of crop water demand and green water availability under warming scenarios, we assess global agricultural green water scarcity—defined when the rainfall regime is unable to meet crop water requirements. With present-day climate conditions, food production for 890 million people is lost because of green water scarcity. Under 1.5°C and 3°C warming—the global warming projected from the current climate targets and business as usual policies—green water scarcity will affect global crop production for 1.23 and 1.45 billion people, respectively. If adaptation strategies were to be adopted to retain more green water in the soil and reduce evaporation, we find that food production loss from green water scarcity would decrease to 780 million people. Our results show that appropriate green water management strategies have the potential to adapt agriculture to green water scarcity and promote global food security.
Immunogenic molecules associated with gut bacterial cell walls: chemical structures, immune-modulating functions, and mechanisms
Authors: Yin Ruopeng , Wang Tao , Dai Huanqin , Han Junjie , Sun Jingzu , Liu Ningning , Dong Wang , Zhong Jin , Liu Hongwei
Published: April 2023

Interactions between gut microbiome and host immune system are fundamental to maintaining the intestinal mucosal barrier and homeostasis. At the host-gut microbiome interface, cell wall-derived molecules from gut commensal bacteria have been reported to play a pivotal role in training and remodeling host immune responses. In this article, we review gut bacterial cell wall-derived molecules with characterized chemical structures, including peptidoglycan and lipid-related molecules that impact host health and disease processes via regulating innate and adaptive immunity. Also, we aim to discuss the structures, immune responses, and underlying mechanisms of these immunogenic molecules. Based on current advances, we propose cell wall-derived components as important sources of medicinal agents for the treatment of infection and immune diseases.
A ‘Polyphonic Score’: Basil Bunting’s Persian Condensations
Authors: Abbas Reem
Published: April 2023

In 1932, Basil Bunting was lodging with the Pounds in Genoa when he first encountered a French manuscript translation of Abul-Qasem Firdausi’s classical Persian epic the Shahnameh (1010). Upon realizing that the manuscript was incomplete, Bunting decided there was ‘nothing to do but learn Persian and read Firdausi, so I undertook that’. By 1942 his knowledge of Persian was good enough for the Ministry of Information to send him to Iran with the Royal Airforce, at which point he toured the Middle East, Central Asia, and parts of Africa. Through these travels, and in particular his time in Iran, he discovered renewed possibilities for his personal and poetic life. His engagement with classical Persian literature over the 1940s was extensive and allowed him to eventually compose masterful translations of canonical classical Persian poets. I argue that his later translations, especially those written from 1947, demonstrate how translating Persian poetry refined Bunting’s Poundian poetics of condensation. I show that this synthesis produced formally and generically pluralistic poems that straddle multiple cultures, such as Odes 35 (1947) and 36 (1948). Through an analysis of The Spoils (1951), I explore the way in which Bunting’s own poetry was inflected by the Arabo-Persian ‘bait’ such that its literary traditions were made resonant with Anglophone ones. I then conclude by illustrating how the translations, the later odes, and The Spoils enabled him to write his irreducibly multiple magnum opus Briggflatts (1965).
Regional Consumption Responses and the Aggregate Fiscal Multiplier
Authors: Dupor Bill , Karabarbounis Marios , Kudlyak Marianna , Saif Mehkari M
Published: April 2023

We use regional variation in the American Recovery and Reinvestment Act (2009–12) to analyse the effect of government spending on consumer spending. Our consumption data come from household-level retail purchases in the Nielsen scanner data and auto purchases from Equifax credit balances. We estimate that a $1 increase in county-level government spending increases local non-durable consumer spending by $0.29 and local auto spending by $0.09. We translate the regional consumption responses to an aggregate fiscal multiplier using a multi-region, new Keynesian model with heterogeneous agents, incomplete markets, and trade linkages. Our model is consistent with the estimated positive local multiplier, a result that distinguishes our incomplete markets model from models with complete markets. At the zero lower bound, the aggregate consumption multiplier is twice as large as the local multiplier because trade linkages propagate the effect of government spending across regions.
Long-Term Monitoring of Aphid-Transmitted Viruses in Melon and Zucchini Crops: Genetic Diversity and Population Structure of Cucurbit Aphid-Borne Yellows Virus and Watermelon Mosaic Virus
Authors: Rabadán M. P. , Juárez M. , Gómez P.
Published: April 2023

Understanding the emergence and prevalence of viral diseases in crops requires the systematic epidemiological monitoring of viruses, as well as the analysis of how ecological and evolutionary processes combine to shape viral population dynamics. Here, we extensively monitored the occurrence of six aphid-transmitted viruses in melon and zucchini crops in Spain for 10 consecutive cropping seasons between 2011 and 2020. The most prevalent viruses were cucurbit aphid-borne yellows virus (CABYV) and watermelon mosaic virus (WMV), found in 31 and 26% of samples with yellowing and mosaic symptoms. Other viruses, such as zucchini yellow mosaic virus, cucumber mosaic virus, Moroccan watermelon mosaic virus, and papaya ring spot virus, were detected less frequently (<3%) and mostly in mixed infections. Notably, our statistical analysis showed a significant association between CABYV and WMV in melon and zucchini hosts, suggesting that mixed infections might be influencing the evolutionary epidemiology of these viral diseases. We then carried out a comprehensive genetic characterization of the full-length genome sequences from CABYV and WMV isolates by using the Pacific Biosciences single-molecule real-time (PacBio) high-throughput technology to assess the genetic variation and structure of their populations. Our results showed that the CABYV population displayed seven codons under positive selection, and although most isolates clustered in the Mediterranean clade, a subsequent analysis of molecular variance revealed a significant, fine-scale temporal structure, which was in part explained by the level of the variance between isolates from single and mixed infections. In contrast, the WMV population genetic analysis showed that most of the isolates grouped into the Emergent clade, with no genetic differentiation and under purifying selection. These results underlie the epidemiological relevance of mixed infections for CABYV and provide a link between genetic diversity and CABYV dynamics at the whole-genome level.
Morphine and Hydromorphone Effects, Side Effects, and Variability: A Crossover Study in Human Volunteers
Authors: Meissner Konrad , Dahan Albert , Olofsen Erik , Göpfert Christine , Blood Jane , Wieditz Johannes , Kharasch Evan D.
Published: April 2023

Background

Balancing between opioid analgesia and respiratory depression continues to challenge clinicians in perioperative, emergency department, and other acute care settings. Morphine and hydromorphone are postoperative analgesic standards. Nevertheless, their comparative effects and side effects, timing, and respective variabilities remain poorly understood. This study tested the hypothesis that IV morphine and hydromorphone differ in onset, magnitude, duration, and variability of analgesic and ventilatory effects.

Methods

The authors conducted a randomized crossover study in healthy volunteers. Forty-two subjects received a 2-h IV infusion of hydromorphone (0.05 mg/kg) or morphine (0.2 mg/kg) 1 to 2 weeks apart. The authors measured arterial opioid concentrations, analgesia in response to heat pain (maximally tolerated temperature, and verbal analog pain scores at discrete preset temperatures to determine half-maximum temperature effect), dark-adapted pupil diameter and miosis, end-expired carbon dioxide, and respiratory rate for 12 h after dosing.

Results

For morphine and hydromorphone, respectively, maximum miosis was less (3.9 [3.4 to 4.2] vs. 4.6 mm [4.0 to 5.0], P < 0.001; median and 25 to 75% quantiles) and occurred later (3.1 ± 0.9 vs. 2.3 ± 0.7 h after infusion start, P < 0.001; mean ± SD); maximum tolerated temperature was less (49 ± 2 vs. 50 ± 2°C, P < 0.001); verbal pain scores at end-infusion at the most informative stimulus (48.2°C) were 82 ± 4 and 59 ± 3 (P < 0.001); maximum end-expired CO2 was 47 (45 to 50) and 48 mmHg (46 to 51; P = 0.007) and occurred later (5.5 ± 2.8 vs. 3.0 ± 1.5 h after infusion start, P < 0.001); and respiratory nadir was 9 ± 1 and 11 ± 2 breaths/min (P < 0.001), and occurred at similar times. The area under the temperature tolerance-time curve was less for morphine (1.8 [0.0 to 4.4]) than hydromorphone (5.4°C-h [1.6 to 12.1] P < 0.001). Interindividual variability in clinical effects did not differ between opioids.

Conclusions

For morphine compared to hydromorphone, analgesia and analgesia relative to respiratory depression were less, onset of miosis and respiratory depression was later, and duration of respiratory depression was longer. For each opioid, timing of the various clinical effects was not coincident. Results may enable more rational opioid selection, and suggest hydromorphone may have a better clinical profile.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Patient-specific Risk Factors Increase Episode of Care Costs After Lumbar Decompression
Authors: D’Antonio Nicholas D. , Lambrechts Mark J. , Trenchfield Delano , Sherman Matthew , Karamian Brian A. , Fredericks Donald J. , Boere Payton , Siegel Nicholas , Tran Khoa , Canseco Jose A. , Kaye Ian David , Rihn Jeffrey , Woods Barrett I. , Hilibrand Alan S. , Kepler Christopher K. , Vaccaro Alexander R. , Schroeder Gregory D.
Published: April 2023

Study Design:

Retrospective cohort analysis.

Objective:

To determine, which patient-specific risk factors increase total episode of care (EOC) costs in a population of Centers for Medicare and Medicaid Services beneficiaries undergoing lumbar decompression.

Summary of Background Data:

Lumbar decompression is an effective option for the treatment of central canal stenosis or radiculopathy in patients unresponsive to nonoperative management. Given that elderly Americans are more likely to have one or more chronic medical conditions, there is a need to determine, which, if any, patient-specific risk factors increase health care costs after lumbar decompression.

Methods:

Care episodes limited to lumbar decompression surgeries were retrospectively reviewed on a Centers for Medicare and Medicaid Service reimbursement database at our academic institution between 2014 and 2019. The 90-day total EOC reimbursement payments were collected. Patient electronic medical records were then matched to the selected care episodes for the collection of patient demographics, medical comorbidities, surgical characteristics, and clinical outcomes. A stepwise multivariate linear regression model was developed to predict patient-specific risk factors that increased total EOC costs after lumbar decompression. Significance was set at P <0.05.

Results:

A total of 226 patients were included for analysis. Risk factors associated with increased total EOC cost included increased age (per year) (β = $324.70, P < 0.001), comorbid depression (β = $4368.30, P = 0.037), revision procedures (β = $6538.43, P=0.012), increased hospital length of stay (per day) (β = $2995.43, P < 0.001), discharge to an inpatient rehabilitation facility (β = $14,417.42, P = 0.001), incidence of a complication (β = $8178.07, P < 0.001), and readmission (β = $18,734.24, P < 0.001) within 90 days.

Conclusions:

Increased age, comorbid depression, revision decompression procedures, increased hospital length of stay, discharge to an inpatient rehabilitation facility, and incidence of a complication and readmission within 90 days were all associated with increased total episodes of care costs.
Comparison of long-term quality of life between Billroth-I and Roux-en-Y anastomosis after distal gastrectomy for gastric cancer: a randomized controlled trial
Authors: Yang Kun , Zhang Weihan , Chen Zehua , Chen Xiaolong , Liu Kai , Zhao Linyong , Hu Jiankun
Published: April 2023

Background:

The results of studies comparing Billroth-I (B-I) with Roux-en-Y (R-Y) reconstruction on the quality of life (QoL) are still inconsistent. The aim of this trial was to compare the long-term QoL of B-I with R-Y anastomosis after curative distal gastrectomy for gastric cancer.

Methods:

A total of 140 patients undergoing curative distal gastrectomy with D2 lymphadenectomy in West China Hospital, Sichuan University from May 2011 to May 2014 were randomly assigned to the B-I group (N = 70) and R-Y group (N = 70). The follow-up time points were 1, 3, 6, 9, 12, 24, 36, 48, and 60 months after the operation. The final follow-up time was May 2019. The clinicopathological features, operative safety, postoperative recovery, long-term survival as well as QoL were compared, among which QoL was the primary outcome. An intention-to-treat analysis was applied.

Results:

The baseline characteristics were comparable between the two groups. There were no significant differences in terms of postoperative morbidity and mortality rates, and postoperative recovery between the two groups. Less estimated blood loss and shorter surgical duration were found in the B-I group. There were no significant differences in 5-year overall survival (79% [55/70] of the B-I group vs. 80% [56/70] of the R-Y group, P = 0.966) and recurrence-free survival rates (79% [55/70] of the B-I group vs. 78% [55/70] of the R-Y group, P = 0.979) between the two groups. The scores of the global health status of the R-Y group were higher than those of the B-I group with statistical differences (postoperative 1 year: 85.4 ± 13.1 vs. 88.8 ± 16.1, P = 0.033; postoperative 3 year: 87.3 ± 15.2 vs. 92.8 ± 11.3, P = 0.028; postoperative 5 year: 90.9 ± 13.7 vs. 96.4 ± 5.6, P = 0.010), and the reflux (postoperative 3 year: 8.8 ± 12.9 vs. 2.8 ± 5.3, P = 0.001; postoperative 5 year: 5.1 ± 9.8 vs. 1.8 ± 4.7, P = 0.033) and epigastric pain (postoperative 1 year: 11.8 ± 12.7 vs. 6.1 ± 8.8, P = 0.008; postoperative 3 year: 9.4 ± 10.6 vs. 4.6 ± 7.9, P = 0.006; postoperative 5 year: 6.0 ± 8.9 vs. 2.7 ± 4.6, P = 0.022) were milder in the R-Y group than those of the B-I group at the postoperative 1, 3, and 5-year time points.

Conclusions:

Compared with B-I group, R-Y reconstruction was associated with better long-term QoL by reducing reflux and epigastric pain, without changing survival outcomes.

Trial Registration:

Chinese Clinical Trial Register (ChiCTR), No. ChiCTR-TRC-10001434.
The future of frozen-thawed embryo transfer in hormone replacement therapy cycles
Authors: Løssl Kristine , Spangmose Anne Lærke , Asserhøj Louise Laub , Dam Tine Vrist , Pinborg Anja
Published: April 2023

Purpose of review

This review focuses on the efficacy of letrozole stimulated frozen-thawed embryo transfer (FET) compared to hormone replacement therapy (HRT) FET in women with polycystic ovarian syndrome (PCOS) and/or oligo-anovulation. Further, obstetric and perinatal risks in HRT FET are summarized.

Recent findings

The presence of a corpus luteum seems to reduce the risk of pregnancy-related hypertension and preeclampsia after FET. As a natural cycle (NC) FET is not an option for women with oligo-/amenorrhea these women may benefit from FET with mild stimulation compared to HRT FET. The intention of mild stimulation in anovulatory women is to induce (mono) ovulation to mimic the endocrine profiles of the natural cycle and the early pregnancy after natural conception. Mild stimulation by letrozole is patient friendly and cheap compared to gonadotropin stimulated FET and has been increasingly used in recent years. Although the quality of evidence is low, the pregnancy outcomes after letrozole FET seems similar or even better compared to HRT FET in women with PCOS and/or oligo-anovulation.

Natural and modified NC FET should be used whenever possible to mitigate adverse obstetric and perinatal outcomes after HRT FET. For anovulatory women, whenever ovulation can be induced, we advocate the use of mild stimulation FET to create a corpus luteum awaiting results from RCTs limited to oligo-anovulatory women.
Need for and extent of lymph node dissection for upper tract urothelial carcinoma: an updated review in 2023
Authors: Yanagisawa Takafumi , Kawada Tatsushi , von Deimling Markus , Laukhtina Ekaterina , Kimura Takahiro , Shariat Shahrokh F.
Published: April 2023

Purpose of review

Although lymph node dissection (LND) during radical nephroureterectomy (RNU) is recommended for high-risk nonmetastatic upper tract urothelial carcinoma (UTUC), adherence to guidelines remains insufficient in clinical practice. Therefore, this review aims to comprehensively summarize the current evidence regarding the diagnostic, prognostic, and therapeutic impact of LND during RNU in UTUC patients.

Recent findings

Clinical nodal staging using conventional CT scan has low sensitivity (25%) and diagnostic accuracy [area under the curve (AUC): 0.58] in UTUC, suggesting the importance of LND for obtaining accurate N-staging. Patients with pathological node-positive (pN+) disease have poor disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) compared with those with pN0. In addition, population-based studies showed that patients who underwent LND improved CSS and OS than those who did not, even in patients who received adjuvant systemic therapy. The number of lymph nodes removed has also been shown to be associated with improved CSS and OS, even in pT0 patients. Template-based LND should be performed as the extent of lymph node is more important than the number of lymph nodes. Robot-assisted RNU may facilitate performing a meticulous LND compared with a laparoscopic approach. Postoperative complications such as lymphatic and/or chylous leakage are increased but adequately manageable. However, the current evidence is not supported by high-quality studies.

Based on the published data, LND during RNU is a standard procedure for high-risk nonmetastatic UTUC, owing to its diagnostic, staging, prognostic, and, potentially, therapeutic benefits. Template-based LND should be offered to all patients who are planned for RNU for high-risk nonmetastatic UTUC. Patients with pN+ disease are optimal candidates for adjuvant systemic therapy. Robot-assisted RNU may facilitate meticulous LND compared with laparoscopic RNU.
Epidemiology and outcomes of traumatic vascular injury repair by trauma surgeons and vascular surgeons in a collaborative model
Authors: Gallagher Shea , Sozzi Marco , Gallegos Hannah , Ugarte Chaiss , Park Stephen , Schellenberg Morgan , Matsushima Kazuhide , Magee Gregory A. , Inaba Kenji , Martin Matthew
Published: April 2023

BACKGROUND

Management roles for peripheral vascular injuries (PVI) are a source of ongoing debate given the concern for the loss of vascular skills among general surgeons and trauma surgeons (TS). We sought to analyze outcomes of PVI managed by TSs or vascular surgeons (VSs).

METHODS

This is a retrospective study of a single, Level I trauma center. Trauma patients with PVI who underwent repair from 2010 to 2021 were included. Patients were separated into groups by the surgical specialty (TS or VS) undertaking the first intervention of the injured vessel.

RESULTS

A total of 194 patients were included, with 101 (52%) PVI managed by TS and 93 (48%) by VS. The TS group had more penetrating injuries (84% vs. 63%, p < 0.01), were more often hypotensive (17% vs. 6%, p = 0.01), and had a higher median Injury Severity Score (10 vs. 9, p < 0.001). Time from arrival to operating room was lower in the TS group (77 vs. 257 minutes, p < 0.01), with no difference in rates of preoperative imaging. The TS group performed damage-control surgery (DCS) more frequently (21% vs. 1.1%, p < 0.01). There was no difference in reintervention rates between the two groups after excluding patients that required reintervention for definitive repair after DCS (13% vs. 9%, p = 0.34). Mortality was 8% in the TS group and 1% in the VS group (p = 0.02) with no deaths related to the PVI repair in either group. There was no difference in PVI repair complication rates between the two groups (18% vs. 13%; p = 0.36).

CONCLUSION

In our collaborative model at a high-volume trauma center, a wide variety of PVI are surgically managed by TS with VS. immediately available for consultation or for definitive repair of more complex vascular injuries. Trauma surgeons performed more DCS on higher acuity patients. No difference in vascular-related complications was detected between groups.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level IV.
Multilevel dynamic adjustments of geckos (
Hemidactylus frenatus
) climbing vertically: head-up versus head-down
Authors: Schultz Johanna T. , Labonte David , Clemente Christofer J.
Published: April 2023

Many climbing animals use direction-dependent adhesives to attach to vertical or inclined surfaces. These structures adhere when activated via a pull but detach when pushed. Therefore, a challenge arises when a change in climbing direction causes external forces such as gravity to change its acting orientation upon the lizard. To investigate how specialized climbers adjust, we studied kinematics and dynamics of six
Hemidactylus frenatus
geckos climbing head-up and head-down a vertical racetrack. We found that limbs functionally swap their adhesive role: feet above the centre of mass (COM) generated adhesive forces, feet below the COM compressive forces, both equal in magnitude across directions. To investigate how lizards perform this swap, despite the constraint of their direction-dependent adhesives, we analysed kinematic adjustments across multiple smaller levels of hierarchy: limbs, feet and toes. All levels contributed: the hindfoot angle was reoriented realigning the adhesive structure, the hindlimb centre range of motion was further protracted and the hindfoot toe spreading was reduced. Notably, all three variables were adjustments of hindlimbs, suggesting that they make a more flexible contribution in upward versus downward climbing, while forelimbs may be anatomically or functionally constrained. The relevance of multilevel dynamic adjustments might inform the development of performant gaits for legged climbing robots.
Onggi’s permeability to carbon dioxide accelerates kimchi fermentation
Authors: Kim Soohwan , Hu David L.
Published: April 2023

Since ancient times, Korean chefs have fermented foods in an onggi, a traditional earthenware vessel. The porous structure of the onggi mimics the loose soil where lactic acid bacteria is naturally found. This permeability has been purported to facilitate the growth of lactic acid bacteria, but the details of the process remain poorly understood. In this combined experimental and theoretical study, we ferment salted napa cabbage in onggi and hermetic glassware and measure the time course of carbon dioxide concentration, which is a signature of fermentation. We present a mathematical model for carbon dioxide generation rate during fermentation using the onggi’s gas permeability as a free parameter. Our model provides a good fit for the data, and we conclude that porous walls help the onggi to ‘exhale’ carbon dioxide, lowering internal levels to those favoured by lactic acid bacteria. The positive pressure inside the onggi and the constant outflow through its walls act as a safety valve for bacteria growth by blocking the entry of external contaminants without mechanical components. We hope this study draws attention to the work of traditional artisans and inspires energy-efficient methods for fermenting and storing food products.
High-resolution recording of foraging behaviour over multiple annual cycles shows decline in old Adélie penguins' performance
Authors: Lescroël Amélie , Schmidt Annie , Ainley David G. , Dugger Katie M. , Elrod Megan , Jongsomjit Dennis , Morandini Virginia , Winquist Suzanne , Ballard Grant
Published: April 2023

Age-related variation in foraging performance can result from both within-individual change and selection processes. These mechanisms can only be disentangled by using logistically challenging long-term, longitudinal studies. Coupling a long-term demographic data set with high-temporal-resolution tracking of 18 Adélie penguins (Pygoscelis adeliae, age 4–15 yrs old) over three consecutive annual cycles, we examined how foraging behaviour changed within individuals of different age classes. Evidence indicated within-individual improvement in young and middle-age classes, but a significant decrease in foraging dive frequency within old individuals, associated with a decrease in the dive descent rate. Decreases in foraging performance occurred at a later age (from 12–15 yrs old to 15–18 yrs old) than the onset of senescence predicted for this species (9–11 yrs old). Foraging dive frequency was most affected by the interaction between breeding status and annual life-cycle periods, with frequency being highest during returning migration and breeding season and was highest overall for successful breeders during the chick-rearing period. Females performed more foraging dives per hour than males. This longitudinal, full annual cycle study allowed us to shed light on the changes in foraging performance occurring among individuals of different age classes and highlighted the complex interactions among drivers of individual foraging behaviour.
Visual integration of GWAS and differential expression results with the hidecan R package
Authors: Angelin-Bonnet Olivia , Vignes Matthieu , Biggs Patrick J. , Baldwin Samantha , Thomson Susan
Published: April 2023

We presenthidecan, an R package for generating visualisations that summarise the results of one or more genome-wide association studies and differential expression analyses, as well as manually curated candidate genes, e.g. extracted from the literature.

Availability and Implementation

The hidecan package is implemented in R and is publicly available on the CRAN repository (https://CRAN.R-project.org/package=hidecan) and on GitHub (https://github.com/PlantandFoodResearch/hidecan). A description of the package, as well as a detailed tutorial are available athttps://plantandfoodresearch.github.io/hidecan/.

Contact

olivia.angelin-bonnet@plantandfood.co.nz.

Supplementary information

Supplementary data are available.
Spatially selective open loop control of magnetic microrobots for drug delivery
Authors: Mirkhani Nima , Christiansen Michael G. , Gwisai Tinotenda , Menghini Stefano , Schuerle Simone
Published: April 2023

Rotating magnetic fields (RMFs), when used to actuate biomedical microrobots for targeted delivery to tumors, have been shown to enable them to overcome physiological barriers and promote their accumulation and penetration into tissue. Nevertheless, directly applying a RMF to a deeply situated target site also leads to off-target actuation in surrounding healthy tissue. Here, we investigate an open-loop control strategy for delivering torque density to diffuse distributions of microrobots at focal points by combining RMFs with magnetostatic gating fields. Taking magnetotactic bacteria (MTB) as a model biohybrid microrobotic system for torque-based actuation, we first use simulation to elucidate off-target torque suppression and find that resolution is set by the relative magnitude of the magnetostatic field and RMF. We study focal torque delivery in vitro, observing off-target suppression of translational velocity of MTB, convection-driven accumulation of companion nanoparticles, and tumor spheroid colonization. We then design, construct, and validate a mouse-scale torque-focusing apparatus incorporating a permanent magnet array, three-phase RMF coils, and offset coils to maneuver the focal point. Our control scheme enables the advantages of torque-based actuation to be combined with spatial targeting, and could be broadly applied to other microrobotic designs for improved drug delivery.

One-Sentence Summary:

Combining rotating magnetic fields with gating fields enables focused delivery of torque density to dispersed microrobots.
Self-Healable Spider Dragline Silk Materials
Authors: Chen Wen-Chia , Wang Ruei-Ci , Yu Sheng-Kai , Chen Jheng-Liang , Kao Yu-Han , Wang Tzi-Yuan , Chang Po-Ya , Sheu Hwo-Shuenn , Chen Ssu Ching , Liu Wei-Ren , Yang Ta-I , Wu Hsuan-Chen
Published: April 2023

Developing materials with structural flexibility that permits self-repair in response to external disturbances remains challenging. Spider silk, which combines an exceptional blend of strength and pliability in nature, serves as an ideal dynamic model for adaptive performance design. In this work, a novel self-healing material is generated using spider silk. Dragline silk from spiderNephila pilipesis demonstrated with extraordinaryin situself-repair property through a constructed thin film format, surpassing that of two other silks from spiderCyrtophora moluccensisand silkwormBombyx mori. Subsequently, R2, a key spidroin associated with self-healing, is biosynthesized, with validated cohesiveness. R2 is further programmed with tunable healability (permanent and reversible) and conductivity (graphene doping; R2G) for electronics applications. In the first demonstration, film strips from R2 and R2G are woven manually into multidimensional (1D-3D) conductive fabrics for creating repairable logic gate circuits. In the second example, a reversibly-healable R2/R2G strip is fabricated as a re-configurable wearable ring probe to fit fingertips of varying widths while retaining its detecting capabilities. Such prototype displays a unique conformable wearable technology. Last, the remarkable finding of self-healing in spider silk could offer a new material paradigm for developing future adaptive biomaterials with tailored performance and environmental sustainability.
Are human connectomes heritable?
Authors: Chung Jaewon , Bridgeford Eric W , Powell Michael , Pisner Derek , Xu Ting , Vogelstein Joshua T
Published: April 2023

A complete understanding of human behavior and disease depends upon our ability to parse genetic and environmental influences in the human brain. The heritability of a trait quantifies the degree of its variability due to genetic influences. Classical approach for quantifying heritability operate on simple traits, and sometimes do not properly model and control for other potential sources of variation, such as age or sex. We therefore develop Causal Heritability of Networks (CHaiN) to rigorously quantify heritability of human brain networks (i.e., connectomes). We applied CHaiN to 1024 anatomical connectomes derived from the Human Connectome Project. Connectomes appeared to be heritable, but heritability was insignificant once we addressed variability within networks. These results suggest that previous conclusions on connectome heritability may be driven by the shared network structures, and highlights the importance of modeling networks and other sources of variability when studying heritability of connectomes.
Differentiation and Integration of Competing Memories: A Neural Network Model
Authors: Ritvo Victoria J. H. , Nguyen Alex , Turk-Browne Nicholas B. , Norman Kenneth A.
Published: April 2023

What determines when neural representations of memories move together (integrate) or apart (differentiate)? Classic supervised learning models posit that, when two stimuli predict similar outcomes, their representations should integrate. However, these models have recently been challenged by studies showing that pairing two stimuli with a shared associate can sometimes cause differentiation, depending on the parameters of the study and the brain region being examined. Here, we provide a purely unsupervised neural network model that can explain these and other related findings. The model can exhibit integration or differentiation depending on the amount of activity allowed to spread to competitors — inactive memories are not modified, connections to moderately active competitors are weakened (leading to differentiation), and connections to highly active competitors are strengthened (leading to integration). The model also makes several novel predictions — most importantly, that when differentiation occurs as a result of this unsupervised learning mechanism, it will be rapid and asymmetric, and it will give rise to anticorrelated representations in the region of the brain that is the source of the differentiation. Overall, these modeling results provide a computational explanation for a diverse set of seemingly contradictory empirical findings in the memory literature, as well as new insights into the dynamics at play during learning.
Paradoxical increases in anterior cingulate cortex activity during nitrous oxide-induced analgesia reveal a signature of pain affect
Authors: Weinrich Jarret AP , Liu Cindy D , Jewell Madison E , Andolina Christopher R , Bernstein Mollie X , Benitez Jorge , Rodriguez-Rosado Sian , Braz Joao M , Maze Mervyn , Nemenov Mikhail I , Basbaum Allan I
Published: April 2023

The general consensus is that increases in neuronal activity in the anterior cingulate cortex (ACC) contribute to pain’s negative affect. Here, usingin vivoimaging of neuronal calcium dynamics in mice, we report that nitrous oxide, a general anesthetic that reduces pain affect, paradoxically, increases ACC spontaneous activity. As expected, a noxious stimulus also increased ACC activity. However, as nitrous oxide increases baseline activity, the relative change in activity from pre-stimulus baseline was significantly less than the change in the absence of the general anesthetic. We suggest that this relative change in activity represents a neural signature of the affective pain experience. Furthermore, this signature of pain persists under general anesthesia induced by isoflurane, at concentrations in which the mouse is unresponsive. We suggest that this signature underlies the phenomenon of connected consciousness, in which use of the isolated forelimb technique revealed that pain percepts can persist in anesthetized patients.
The autophagy protein Atg9 functions in glia and contributes to parkinsonian symptoms in aDrosophilamodel of Parkinson’s disease
Authors: Yi Shuanglong , Wang Linfang , Ho Margaret S. , Zhang Shiping
Published: April 2023

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the motor deficits, selective loss of dopaminergic (DA) neurons, and the brain accumulation of α-synuclein (α-syn)-composed protein aggregates called Lewy bodies (LBs). Whereas dysfunction in the protein degradation pathway, like autophagy in neurons, has been demonstrated as a critical mechanism for eliminating protein aggregates in PD, how protein aggregates are eliminated in the other brain cell type, glia, is less well characterized. In the present study, we show that Atg9, the only transmembrane protein in the core autophagy pathway, is highly expressed inDrosophilaadult brain glia. Results from immunostaining and live-cell imaging analysis reveal that a significant portion of Atg9 localizes to the trans-Golgi network (TGN), autophagosomes, and lysosomes in glia; Atg9 is persistently in contact with these organelles. Lacking glialatg9reduces the number of omegasome and autophagosome and impairs autophagic substrate degradation, suggesting that glial Atg9 participates in the early steps of autophagy, hence the control of autophagic degradation. Importantly, loss of glialatg9induces parkinsonian symptoms inDrosophilaincluding progressive DA neuron loss and locomotion deficits. Our findings identify a functional role of Atg9 in glial autophagy and establish a potential link between glial autophagy and PD. These results provide new insights on the underlying mechanism of PD.