bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative efficacy of various exercise types and doses for depression in older adults: a systematic review of paired, network and dose–response meta-analyses
Authors: Tian Shudong , Liang Zhide , Tian Mengmeng , Qiu Fanghui , Yu Yingdanni , Mou Hong , Gao Yan
Published: October 2024

Objectives

We assessed the effects of different exercise modalities and doses on depression levels in older adults.

Methods

Systematic searches of the PubMed, Web of Science, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Scopus databases were conducted from the start of database construction until December 2023. Studies were included if they were randomised controlled trials (RCTs) of exercise interventions in older adults. Pairwise, network and dose-network meta-analyses were conducted using random-effects models for the outcome of depression in older adults.

Results

A total of 80 RCTs with 5536 participants were included in this study. Network meta-analyses showed that resistance exercise [standardized mean difference (SMD) = − 0.68, 95% confidence interval (CI): − 0.90, − 0.46] and mind–body exercise (MBE; SMD = − 0.54, 95% CI: − 0.72, − 0.37) were the most effective forms of exercise for improving depression in older adults, followed by aerobic exercise (SMD = − 0.31, 95% CI: − 0.50, − 0.13) and mixed exercise (SMD = − 0.23, 95% CI: − 44, − 0.01). In addition, a U-shaped dose–response relationship was found between overall exercise dose and depression levels in older adults, and a significant response was seen after 390 metabolic equivalent (MET)-min/week.

Conclusions

Our study determined the effectiveness of different exercises in improving levels of older adults and found that resistance exercise and MBE were more effective adjunctive treatments. By providing the most effective treatments, older adults can reap the benefits of improving depression in older adults at doses lower than the World Health Organization guidelines.
Energy-Based Medical Devices in Plastic Surgery: A Comparison of FDA-Approved Indications to Advertised Claims
Authors: Gomez Diego A , Abdulwadood Isra , Bogan Aaron , Morris Bryn E , Kenkel Jeffrey M , Bernard Robert W , Reece Edward M
Published: October 2024

Background

Lasers and energy-based devices are commonly employed in aesthetic medicine. In the United States, the FDA regulates lasers as medical devices, restricting marketing to approved indications and making off-label claims illegal. Despite this, no comprehensive analysis of off-label marketing prevalence exists.

Objectives

The authors of this study aim to compare the FDA-approved indications for 2 popular aesthetic lasers to their online advertising claims. Additionally, they seek to educate aesthetic providers on the current regulatory restrictions surrounding off-label advertising.

Methods

FDA-approved indications for 2 lasers—helium plasma dermal resurfacing and 2940 nm fractional erbium-doped yttrium aluminum garnet—were obtained from the publicly available Establishment Registration & Device Listings Database. Online advertisements regarding the capabilities of each laser were collected from practice websites in the United States.

Results

Our analysis of 100 online claims for each laser revealed that more than half of the websites advertising helium plasma (n = 59) and 44 websites advertising fractional lasers made at least 1 off-label claim. Both plastic surgeons and nonplastic surgeons made at least 1 off-label claim, with no statistically significant difference between the groups.

Conclusions

Despite FDA regulation of medical devices, online advertising regarding the indications and capabilities of popular medical lasers varies widely. Patients who seek information regarding aesthetic laser treatments may encounter inaccurate and differing claims for these treatments, potentially leading to false expectations and poor patient outcomes.

Level of Evidence: 4 (Risk)
Feeling (Un)safe in Prison: A Comparative Analysis of England & Wales and Norway
Authors: Martens Sophie , Crewe Ben
Published: October 2024

While there is abundant literature on prison violence, much less has been written about how safety is perceived and conceived in prison. Even less is known about how these feelings of safety and their respective predictors may vary between prison systems. This study illustrates what predicts feelings of safety and how prisoners define and experience safety in two jurisdictions, Norway and England & Wales. The research employs a mixed-methods approach, using data from surveys (N = 984) and interviews (N = 199) from a major comparative penological project. It finds that while prisoners in Norway generally reported feeling safer than prisoners in England & Wales, the quantitative predictors of safety did not vary by jurisdiction. From a qualitative perspective, however, it was observed that prisoners in England & Wales held a more limited definition of safety (bounded safety) in which they accepted a constant need for vigilance, whereas prisoners in Norway showed more trust in their environment. This finding suggests that feelings of safety in prison may be (at least partly) context-dependent, which raises important questions regarding the much-debated ‘safety paradox’ in prison, and forms a relevant insight for future comparative work.
Different taste map for amiloride sensitivity, response frequency, and threshold to NaCl in the rostral nucleus of the solitary tract in rats
Authors: Yokota Tatsuko , Hiraba Katsunari
Published: October 2024

Studies on taste bud cells and brain stem relay nuclei suggest that alternative pathways convey information regarding different taste qualities. Building on the hypothesis that amiloride (epithelial Na channel antagonist)-sensitive neurons respond to palatable salt (low-concentration) and amiloride-insensitive neurons respond to aversive salt (high-concentration), we investigated the histological distribution of taste-sensitive neurons in the rostral nucleus of the solitary tract in rats and their NaCl and amiloride sensitivities. We recorded neuronal activity in extracellular single units using multi-barrel glass micropipettes and reconstructed their locations on the rostrocaudal and mediolateral axes. Seventy-three taste-sensitive neurons were categorized into the best-taste category. The amiloride sensitivities of the 31 neurons were examined for 0.1, 0.2, 0.4, and 0.8 M NaCl. The neuronal distribution of amiloride-sensitive neurons was located in the lateral region, while amiloride-insensitive neurons were located in the medial region. The amiloride-sensitive neurons responded to low salt concentrations, signaling the NaCl levels required by body fluids. Amiloride-insensitive neurons were silent at low salt concentrations but may function as warning signals for high salt concentrations. Low-threshold and/or high-response neurons were located in the rostrolateral region. In contrast, high-threshold and/or low-response neurons were located in the caudal-medial region.
Unraveling Sepsis Epidemiology in a Low- and Middle-Income Intensive Care Setting Reveals the Alarming Burden of Tropical Infections and Antimicrobial Resistance: A Prospective Observational Study (MARS-India)
Authors: Virk Harjeet S , Biemond Jason J , Earny Venkat A , Chowdhury Soumi , Frölke Roos I , Khanna Saachi M , Shanbhag Vishal , Rao Shwethapriya , Acharya Raviraj V , Balakrishnan Jayaraj M , Eshwara Vandana K , Varma Muralidhar D , van der Poll Tom , Wiersinga Willem J , Mukhopadhyay Chiranjay
Published: October 2024

Background

Our study addresses the sepsis research gap in lower- and middle-income countries, notably India. Here, we investigate community-acquired sepsis comprehensively and explore the impact of tropical microbiology on etiology and outcomes.

Methods

MARS-India was a prospective observational study from December 2018 to September 2022 in a tertiary-care hospital in South India. Adult patients within 24 hours of intensive care unit (ICU) admission meeting the Sepsis-3 definition were enrolled, with 6 months of follow-up.

Results

More than 4000 patients were screened on ICU admission, with 1000 unique patients meeting the inclusion criteria. Median age was 55 (interquartile range, 44–65) years, with a male preponderance (66%). Almost half the cohort resided in villages (46.5%) and 74.6% worked in the primary sector. Mortality in-hospital was 24.1%. Overall, about 54% had confirmed microbiological diagnosis and >18% had a viral cause of sepsis. Surprisingly, we identified leptospirosis (10.6%), scrub typhus (4.1%), dengue (3.7%), and Kyasanur forest disease (1.6%) as notable causes of sepsis. All of these infections showed seasonal variation around the monsoon. In community-acquired infections, we observed substantial resistance to third-generation cephalosporins and carbapenems.

Conclusions

In India, sepsis disproportionally affects a younger and lower-socioeconomic demographic, yielding high mortality. Tropical and viral sepsis carry a significant burden. Analyzing local data, we pinpoint priorities for public health and resources, offering valuable insights for global sepsis research.

Clinical Trials Registration. NCT03727243.
Multielectrode catheter-based pulsed field ablation of persistent and long-standing persistent atrial fibrillation
Authors: Della Rocca Domenico G , Sorgente Antonio , Pannone Luigi , Cespón-Fernández María , Vetta Giampaolo , Almorad Alexandre , Bala Gezim , Del Monte Alvise , Ströker Erwin , Sieira Juan , Doundoulakis Ioannis , Mouram Sahar , Audiat Charles , Monaco Cinzia , Mohanty Sanghamitra , Scacciavillani Roberto , Marcon Lorenzo , Nakasone Kazutaka , Zaher Wael , Overeinder Ingrid , Boveda Serge , La Meir Mark , Natale Andrea , Sarkozy Andrea , de Asmundis Carlo , Chierchia Gian-Battista
Published: October 2024

Aims

Rhythm control of non-paroxysmal atrial fibrillation (AF) is significantly more challenging, as a result of arrhythmia perpetuation promoting atrial substrate changes and AF maintenance. We describe a tailored ablation strategy targeting multiple left atrial (LA) sites via a pentaspline pulsed field ablation (PFA) catheter in persistent AF sustained beyond 6 months (PerAF > 6 m) and long-standing persistent AF (LSPAF).

Methods and results

The ablation protocol included the following stages: pulmonary vein antral and posterior wall isolation plus anterior roof line ablation (Stage 1); electrogram-guided substrate ablation (Stage 2); atrial tachyarrhythmia regionalization and ablation (Stage 3). Seventy-two [age:68 ± 10years, 61.1%males; AF history: 25 (18–45) months] patients with PerAF > 6 m (52.8%) and LSPAF (47.2%) underwent their first PFA via the FarapulseTM system. LA substrate ablation (Stage 1 and 2) led to AF termination in 95.8% of patients. AF organized into a left-sided atrial flutter (AFlu) in 46 (74.2%) patients. The PFA catheter was used to identify LA sites showing diastolic, low-voltage electrograms and entrainment from its splines was performed to confirm the pacing site was inside the AFlu circuit. Left AFlu termination was achieved in all cases via PFA delivery. Total procedural and LA dwell times were 112 ± 25 min and 59 ± 22 min, respectively. Major complications occurred in 2 (2.8%) patients. Single-procedure success rate was 74.6% after 14.9 ± 2.7 months of follow-up; AF-free survival was 89.2%.

Conclusion

In our cohort, PFA-based AF substrate ablation led to AF termination in 95.8% of cases. Very favourable clinical outcomes were observed during >1 year of follow-up.
Improved outcomes with leadless vs. single-chamber transvenous pacemaker in haemodialysis patients
Authors: Panico Alexandre , Flahault Adrien , Guillemin Francis , Varlet Emilie , Couchoud Cécile , Bauwens Marc , Marijon Eloi , Roueff Stéphane , Lazareth Hélène
Published: October 2024

Aims

Cardiac conduction disorders are common in haemodialysis patients, with a relatively high rate of pacemaker implantations. Pacemaker-related complications, especially lead infections and central venous stenosis, pose significant challenges in this population. This study aims to compare single-chamber leadless pacemaker to single-chamber transvenous pacemakers in terms of survival and related complications in haemodialysis patients.

Methods and results

This retrospective study included adult haemodialysis patients who received a first single-chamber transvenous or leadless pacemaker between January 2017 and December 2020. Data were obtained from the French national REIN registry matched to the national health databases (Système National des Données de Santé). Propensity score matching was used to balance baseline characteristics. Survival and complications were compared between groups by Cox regression and by competitive risk models, respectively. One hundred and seventy-eight patients were included after propensity score matching, with 89 patients in each group. The median follow-up time was 24 (range 7–37) months. Leadless pacemakers were associated with significantly lower all-cause mortality rates compared to transvenous pacemakers [hazard ratio (HR) = 0.68, 95% confidence interval (CI) (0.47–0.99)]. Device-related infections are significantly lower with leadless pacemakers throughout the follow-up period (HR 0.43, 95% CI 0.21–0.86). Leadless pacemaker recipients also required fewer vascular access interventions [odds ratio 0.53, 95% CI (0.33–0.68)] on arteriovenous fistula.

Conclusion

With the limitations of its observational design, this study suggests that leadless pacemakers are associated with a lower rate of complications and better survival as compared with transvenous VVI pacemakers in haemodialysis patients, supporting to consider their preferential use in this population.
Compromised CDK12 activity causes dependency on the high activity of O-GlcNAc transferase
Authors: Pallasaho Satu , Gondane Aishwarya , Kutz Julia , Liang Jing , Yalala Shivani , Duveau Damien Y , Pospiech Helmut , Thomas Craig J , Loda Massimo , Itkonen Harri M
Published: October 2024

O-GlcNAc transferase (OGT) coordinates with regulators of transcription, including cyclin-dependent kinase 12 (CDK12), the major transcription elongation kinase. Here, we use inhibitor- and knockdown-based strategies to show that co-targeting of OGT and CDK12 is toxic to prostate cancer cells. OGT catalyzes all nucleocytoplasmic O-GlcNAcylation and due to its essentiality in higher eukaryotes, it is not an ideal drug target. Our glycoproteomics-data revealed that short-term CDK12 inhibition induces hyper-O-GlcNAcylation of the spliceosome-machinery in different models of prostate cancer. By integrating our glycoproteomics-, gene essentiality- and clinical-data from CDK12 mutant prostate cancer patients, we identify the non-essential serine-arginine protein kinase 1 (SRPK1) as a synthetic lethal partner with CDK12-inactivation. Both normal and cancer cells become highly sensitive against inhibitors of OGT and SRPK1 if they have lowered activity of CDK12. Inactivating mutations in CDK12 are enriched in aggressive prostate cancer, and we propose that these patients would benefit from therapy targeting the spliceosome.
The nineties in 1990s Britain: long-sighted temporalities at the turn of the millennium
Authors: Geiringer David
Published: October 2024

Chronological categories of periodization such as decades, centuries and millennia are broadly treated with scepticism by historians. This essay reframes the questions we ask of such categories by exploring their contemporary significance for ‘ordinary’ historical actors. It focuses on the curious case of 1990s Britain, a decade that, in comparison to the historiographical advents of the 1960s, 1970s and 1980s, has been slow to emerge as a distinct trope of periodization. In considering why this might be, the essay looks beyond explanations that focus on the political legacy of Blairism, the stasis of neo-liberal hegemony or the retrospective notion that the decade marked a ‘holiday from history’ – an oasis of consensus, tranquillity and indeed boredom sandwiched between the class and cold wars of the 1980s and a post-9/11 clash of civilizations. Instead, it examines how the nineties were being constructed, contested and wielded in the 1990s themselves. Drawing on materials generated by the sociological organization the Mass Observation Project (M.O.P.), narratives of past, present and future co-produced by ‘ordinary’ observers and the authors of the M.O.P. directives, the article traces the shifting constellation of decadal temporalities that circulated during the nineties. As the decade drew to a close, the spectre of the millennium encouraged a lengthening of imagined temporal trajectories: eyes were cast beyond the immediately surrounding years to the larger terrain of the century and even the millennium. These long-sighted temporalities obscured the nineties as a category of historical significance, shaping the source base and collective memory of the decade. Ultimately, a study of the temporal regimes operating in 1990s Britain reveals the cultural power and emotional stickiness of seemingly arbitrary chronological markers.
Modelling the influence of vitamin D and probiotic supplementation on the microbiome and immune response
Authors: Franks S J , Dunster J L , Carding S R , Lord J M , Hewison M , Calder P C , King J R
Published: October 2024

The intestinal microbiota play a critical role in human health and disease, maintaining metabolic and immune/inflammatory health, synthesizing essential vitamins and amino acids and maintaining intestinal barrier integrity. The aim of this paper is to develop a mathematical model to describe the complex interactions between the microbiota, vitamin D/vitamin D receptor (VDR) pathway, epithelial barrier and immune response in order to understand better the effects of supplementation with probiotics and vitamin D. This is motivated by emerging data indicating the beneficial effects of vitamin D and probiotics individually and when combined. We propose a system of ordinary differential equations determining the time evolution of intestinal bacterial populations, concentration of the VDR:1,25(OH)$_{2}$D complex in epithelial and immune cells, the epithelial barrier and the immune response. The model shows that administration of probiotics and/or vitamin D upregulates the VDR complex, which enhances barrier function and protects against intestinal inflammation. The model also suggests co-supplementation to be superior to individual supplements. We explore the effects of inflammation on the populations of commensal and pathogenic bacteria and the vitamin D/VDR pathway and discuss the value of gathering additional experimental data motivated by the modelling insights.
Machine learning for adverse event prediction in outpatient parenteral antimicrobial therapy: a scoping review
Authors: Challener Douglas W , Fida Madiha , Martin Peter , Rivera Christina G , Virk Abinash , Walker Lorne W
Published: October 2024

Objective

This study aimed to conduct a scoping review of machine learning (ML) techniques in outpatient parenteral antimicrobial therapy (OPAT) for predicting adverse outcomes and to evaluate their validation, implementation and potential barriers to adoption.

Materials and methods

This scoping review included studies applying ML algorithms to adult OPAT patients, covering techniques from logistic regression to neural networks. Outcomes considered were medication intolerance, toxicity, catheter complications, hospital readmission and patient deterioration. A comprehensive search was conducted across databases including Cochrane Central, Cochrane Reviews, Embase, Ovid MEDLINE and Scopus, from 1 January 2000 to 1 January 2024.

Results

Thirty-two studies met the inclusion criteria, with the majority being single-centre experiences primarily from North America. Most studies focused on developing new ML models to predict outcomes such as hospital readmissions and medication-related complications. However, there was very little reporting on the performance characteristics of these models, such as specificity, sensitivity and C-statistics. There was a lack of multi-centre or cross-centre validation, limiting generalizability. Few studies advanced beyond traditional logistic regression models, and integration into clinical practice remains limited.

Discussion

ML shows promise for enhancing OPAT outcomes by predicting adverse events and enabling pre-emptive interventions. Despite this potential, significant gaps exist in development, validation and practical implementation. Barriers include the need for representative data sets and broadly applicable, validated models.

Conclusion

Future research should address these barriers to fully leverage ML’s potential in optimizing OPAT care and patient safety. Models must deliver timely, accurate and actionable insights to improve adverse event prediction and prevention in OPAT settings.
Advances in the clinical treatment of multidrug-resistant pathogens using polymyxins
Authors: Huang Yizhen , Liao Mingrui , Hu Xuzhi , Hu Honghua , Gong Haoning
Published: October 2024

Objectives

Polymyxins are a vital class of antibiotics used to combat multidrug-resistant Gram-negative bacteria. However, their use is limited due to potential nephrotoxicity and the availability of alternative antibiotics. This review aims to examine the properties of polymyxins and the clinical advances in their use for treating infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB).

Methods

This review analyses literature on polymyxin properties and various clinical approaches, including intravenous drip infusion, nebulized or dry powder inhalation, and ointment application. Treatment efficacy in terms of bacterial eradication, cure rate and mortality rate are reviewed and evaluated.

Results

Polymyxins have been reintroduced to treat critical infections due to the increasing prevalence of CR-GNB. Clinical trials and studies have confirmed that polymyxins can effectively treat CR-GNB infections when the formulation and administration are appropriate, with acceptable levels of nephrotoxicity.

Conclusions

In the future, the development of polymyxin formulations will aim to improve their clinical effectiveness while reducing toxicity and side effects and preventing the emergence of polymyxin-resistant strains. Enhanced efficacy and minimized potential side effects can be achieved by developing new polymyxin-delivery systems that provide a smart and controlled release or customized patient administration.
The antimicrobial peptide Microcin C7 inhibits the growth of Porphyromonas gingivalis and improves the periodontal status in a rat model
Authors: Liu Na , Zhang Qianqian , Li Jinyang , Zhou Shuo , Miao Di , Zhang Sijia , Chen Yue
Published: October 2024

Aims

This study aimed to investigate the antibacterial and anti-inflammatory effects of the antimicrobial peptide Microcin C7 for Porphyromonas gingivalis-associated diseases.

Methods and results

Reverse-phase high-performance liquid chromatography revealed that Microcin C7 could remain 25.5% at 12 h in saliva. At a concentration of <10 mg ml–1, Microcin C7 showed better cytocompatibility, as revealed by a hemolysis test and a subchronic systemic toxicity test. Moreover, the minimum inhibitory concentration and minimum bactericidal concentration of Microcin C7 were analyzed using a broth microdilution method, bacterial growth curve, scanning electron microscopy, and confocal laser microscopy and determined to be 0.16 and 5 mg ml–1, respectively. Finally, in a rat model, 5 mg ml–1 Microcin C7 showed better performance in decreasing the expression of inflammatory factors (IL-1β, IL-6, IL-8, and TNF-α) and alveolar bone resorption than other concentrations.

Conclusions

Microcin C7 demonstrated favorable biocompatibility, antibacterial activity, and anti-inflammatory effect, and could decrease the alveolar bone resorption in a rat model, indicating the promising potential for clinical translation and application on P. gingivalis-associated diseases.
When is prostate cancer really cancer?
Authors: Cooperberg Matthew R , Braun Avery E , Berlin Alejandro , Kibel Adam S , Eggener Scott E ,   CANCER-GG1 Writing Group, Paner Gladell P , Nikiforov Yuri E , Esserman Laura J , van der Kwast Theo , Simko Jeff , Lamb Alastair D , Klotz Laurence , Murphy Declan G , Moore Caroline M , Etzioni Ruth , Vickers Andrew , Tilki Derya , Jalloh Mohamed , Trinh Quoc , Yamoah Kosj , Wolinsky Howard , Izdebski Leszek , Stimpson C J , Ryan Charles J , Wilt Timothy J , Ahmed Hashim U , Feng Felix Y
Published: October 2024

Prostate cancer (PC) is a major cause of cancer-related deaths worldwide, with far more diagnoses than deaths annually. Recent discussions have challenged whether Grade Group 1 (GG1) PC should be labeled “cancer” due to its indolent nature. To address this question, an international symposium convened stakeholders from various fields. We summarize key discussion points: autopsy studies reveal GG1 is so common in aging males as to be perhaps a normal aspect of aging. Pure GG1 has no capacity to metastasize. Modern diagnostic pathways focus on detecting higher-grade disease, explicitly omitting biopsy if GG 2 or higher is not suspected, so GG1 has effectively become an “incidentaloma.” Recent spatial transcriptomics of prostate sections identifies a continuum of genomic changes—including alterations characteristic of malignancy in histologically normal regions, so the designation of cancer based entirely on conventional pathology findings increasingly seems arbitrary at least to an extent. Pathologists discussed heterogeneity and diagnostic challenges, suggesting “acinar neoplasm” as one possible alternative label. GG1 should not be considered “normal,” and absolutely requires ongoing active surveillance; whether patients would adhere to surveillance absent a cancer diagnosis is unknown. Patient perspectives highlighted the adverse effects of overtreatment and the burden of a cancer diagnosis. The anticipated impact on screening and treatment varies across health-care systems, but many believe public health would on balance greatly improve if GG1—along with lesions in other organs with no capacity to cause symptoms or threaten life—were labeled something other than “cancer.” Ultimately, our goal is to reduce PC mortality while minimizing harms associated with both overdiagnosis and overtreatment.
Freedom of expression: Our pledge
Authors: Britten Anna
Published: October 2024

In the September issue, we introduced a statement on our editorial page about Significance and freedom of expression. Anna Britten explains why
Unexpected intraoperative finding of a hyalinizing cholecystitis in a patient with gallbladder calculi
Authors: Gjinoska Klaudia , Nikolovski Andrej , Stoicovski Emil , Mitrev Zan
Published: October 2024

Hyalinizing cholecystitis is a rare subtype of chronic cholecystitis in which the gallbladder tissue is replaced with hyaline sclerosis, more or less, and has a characteristic intraoperative appearance. Preoperative diagnosis is hard to establish. The entity is strongly associated with gallbladder carcinoma. Therefore, the pathologist should perform a thorough microscopic analysis. We present a case of an unusual intraoperative finding in a male patient with chronic cholecystitis which was proved to be a hyalinizing cholecystitis.
The PAU survey: photometric redshift estimation in deep wide fields
Authors: Navarro-Gironés D , Gaztañaga E , Crocce M , Wittje A , Hildebrandt H , Wright A H , Siudek M , Eriksen M , Serrano S , Renard P , Gonzalez E J , Baugh C M , Cabayol L , Carretero J , Casas R , Castander F J , Daza-Perilla I V , De Vicente J , Fernandez E , García-Bellido J , Hoekstra H , Manzoni G , Miquel R , Padilla C , Sánchez E , Sevilla-Noarbe I , Tallada-Crespí P
Published: October 2024

We present photometric redshifts (photo-z) for the deep wide fields of the Physics of the Accelerating Universe Survey (PAUS), covering an area of $\sim$50 deg$^{2}$, for $\sim$1.8 million objects up to $i_{\rm {AB}}\lt 23$. The PAUS deep wide fields overlap with the W1 and W3 fields from CFHTLenS and the G09 field from KiDS/GAMA. Photo-z are estimated using the 40 narrow bands (NB) of PAUS and the broad-bands (BB) of CFHTLenS and KiDS. We compute the redshifts with the SED template-fitting code bcnz, with a modification in the calibration technique of the zero-point between the observed and the modelled fluxes, that removes any dependence on spectroscopic redshift samples. We enhance the redshift accuracy by introducing an additional photo-z estimate ($z_{\textrm {b}}$), obtained through the combination of the bcnz and the BB-only photo-z. Comparing with spectroscopic redshift estimates ($z_{\textrm {s}}$), we obtain a $\sigma _{68} \simeq 0.020$ for all galaxies with $i_{\rm {AB}}\lt 23$ and a typical bias $|z_{\textrm {b}}\!-\!z_{\textrm {s}}|$ smaller than 0.01. For $z_{\textrm {b}} \sim (0.10\!-\!0.75)$, we find $\sigma _{68} \simeq (0.003\!-\!0.02)$, this is a factor of $10\!-\!2$ higher accuracy than the corresponding BB-only results. We obtain similar performance when we split the samples into red (passive) and blue (active) galaxies. We validate the redshift probability $p(z)$ obtained by bcnz and compare its performance with that of $z_{\textrm {b}}$. These photo-z catalogues will facilitate important science cases, such as the study of galaxy clustering and intrinsic alignment at high redshifts ($z \lesssim 1$) and faint magnitudes.
Nuclease-induced stepwise photodropping (NISP) to precisely investigate single-stranded DNA degradation behaviors of exonucleases and endonucleases
Authors: Chiu Hui-Pin , Shen Chung-Han , Wu Jan-Kai , Mao Eric Y C , Yen Han-Yi , Chang Yuan-Pin , Wu Chyuan-Chuan , Fan Hsiu-Fang
Published: October 2024

Here, we employed a fluorescence-based single molecule method called nuclease-induced stepwise photodropping (NISP) to measure in real time the DNA degradation mediated by mitochondrial genome maintenance exonuclease 1 (MGME1), a bidirectional single-stranded DNA (ssDNA)-specific exonuclease. The method detects a stepwise decrease in fluorescence signals from Cy3 fluorophores labeled on an immobilized DNA substrate. Using NISP, we successfully determined the DNA degradation rates of 6.3 ± 0.4 and 2.0 ± 0.1 nucleotides (nt) s–1 for MGME1 in the 5′-to-3′ and 3′-to-5′ directions, respectively. These results provide direct evidence of the stronger 5′ directionality of MGME1, consistent with its established role in mitochondrial DNA maintenance. Importantly, when we employed NISP to investigate mung bean nuclease, an ss-specific endonuclease, we observed a markedly different NISP pattern, suggesting a distributive cleavage activity of the enzyme. Furthermore, we applied NISP to determine the ssDNA degradation behavior of the double-stranded-specific exonuclease, λ exonuclease. These findings underscore the capability of NISP to accurately and reliably measure the degradation of ssDNA by both exo- and endonucleases. Here, we demonstrate NISP as a powerful tool for investigating the ssDNA degradation behavior of nucleases at the single-molecule level.
Protein–RNA interactions mediated by silvestrol—insight into a unique molecular clamp
Authors: Naineni Sai Kiran , Bhatt Garvit , Jiramongkolsiri Ekkanat , Robert Francis , Cencic Regina , Huang Sidong , Nagar Bhushan , Pelletier Jerry
Published: October 2024

Molecular staples or interfacial inhibitors are small molecules that exert their activity through co-association with macromolecules leading to various effects on target functions. Some molecules inhibit target activity, while others generate gain-of-function complexes. We and others have previously identified two structurally distinct classes of molecular staples, pateamine A and rocaglates. These molecules inhibit eukaryotic initiation factor (eIF) 4A, a critical RNA helicase required for translation initiation, by simultaneously interacting with both RNA and protein components. Structural insights from members of these two families indicate that they wedge themselves between RNA bases during engagement. To extend our understanding of rocaglates, we investigated the RNA-binding properties of silvestrol, a natural rocaglate distinguished by the presence of a unique dioxanyloxy ring. Our study demonstrates that silvestrol expands the RNA-binding repertoire of rocaglates due to this structural characteristic, providing a rationale for improving synthetic molecular staples targeting eIF4A.
Haplotype-resolved de novo assembly revealed unique characteristics of alternative lengthening of telomeres in mouse embryonic stem cells
Authors: Lee Hyunji , Niida Hiroyuki , Sung Sanghyun , Lee Junho
Published: October 2024

Telomeres protect chromosome ends from DNA damage responses, and their dysfunction triggers genomic alterations like chromosome fusion and rearrangement, which can lead to cellular death. Certain cells, including specific cancer cells, adopt alternative lengthening of telomere (ALT) to counteract dysfunctional telomeres and proliferate indefinitely. While telomere instability and ALT activity are likely major sources of genomic alteration, the patterns and consequences of such changes at the nucleotide level in ALT cells remain unexplored. Here we generated haplotype-resolved genome assemblies for type I ALT mouse embryonic stem cells, facilitated by highly accurate or ultra-long reads and Hi-C reads. High-quality genome revealed ALT-specific complex chromosome end structures and various genomic alterations including over 1000 structural variants (SVs). The unique sequence (mTALT) used as a template for type I ALT telomeres showed traces of being recruited into the genome, with mTALT being replicated with remarkably high accuracy. Subtelomeric regions exhibited distinct characteristics: resistance to the accumulation of SVs and small variants. We genotyped SVs at allele resolution, identifying genes (Rgs6, Dpf3 and Tacc2) crucial for maintaining ALT telomere stability. Our genome assembly-based approach elucidated the unique characteristics of ALT genome, offering insights into the genome evolution of cells surviving telomere-derived crisis.
N
2-Alkyl-dG lesions elicit R-loop accumulation in the genome
Authors: Wang Yinan , Tang Feng , Zhao Ting , Yuan Jun , Kellum Andrew H , Wang Yinsheng
Published: October 2024

Humans are exposed to DNA alkylating agents through endogenous metabolism, environmental exposure and cancer chemotherapy. The resulting alkylated DNA adducts may elicit genome instability by perturbing DNA replication and transcription. R-loops regulate various cellular processes, including transcription, DNA repair, and telomere maintenance. However, unscheduled R-loops are also recognized as potential sources of DNA damage and genome instability. In this study, by employing fluorescence microscopy and R-loop sequencing approaches, we uncovered, for the first time, that minor-groove N2-alkyl-dG lesions elicit elevated R-loop accumulation in chromatin and in plasmid DNA in cells. We also demonstrated that the N2-alkyl-dG-induced R-loops impede transcription elongation and compromise genome integrity. Moreover, genetic depletion of DDX23, a R-loop helicase, renders cells more sensitive toward benzo[a]pyrene diolepoxide, a carcinogen that induces mainly the minor-groove N2-dG adduct. Together, our work unveiled that unrepaired minor-groove N2-alkyl-dG lesions may perturb genome integrity through augmenting R-loop levels in chromatin. Our findings suggest a potential therapeutic strategy involving the combination of R-loop helicase inhibitors with DNA alkylating drugs.
Ribosome Quality Control mitigates the cytotoxicity of ribosome collisions induced by 5-Fluorouracil
Authors: Chatterjee Susanta , Naeli Parisa , Onar Okan , Simms Nicole , Garzia Aitor , Hackett Angela , Coyle Kelsey , Harris Snell Patric , McGirr Tom , Sawant Tanvi Nitin , Dang Kexin , Stoichkova Zornitsa Vasileva , Azam Yumna , Saunders Mark P , Braun Michael , Alain Tommy , Tuschl Thomas , McDade Simon S , Longley Daniel B , Gkogkas Christos G , Adrain Colin , Knight John R P , Jafarnejad Seyed Mehdi
Published: October 2024

Ribosome quality control (RQC) resolves collided ribosomes, thus preventing their cytotoxic effects. The chemotherapeutic agent 5-Fluorouracil (5FU) is best known for its misincorporation into DNA and inhibition of thymidylate synthase. However, while a major determinant of 5FU’s anticancer activity is its misincorporation into RNAs, the mechanisms by which cancer cells overcome the RNA-dependent 5FU toxicity remain ill-defined. Here, we report a role for RQC in mitigating the cytotoxic effects of 5FU. We show that 5FU treatment results in rapid induction of the mTOR signalling pathway, enhanced rate of mRNA translation initiation, and increased ribosome collisions. Consistently, a defective RQC exacerbates the 5FU-induced cell death, which is mitigated by blocking mTOR pathway or mRNA translation initiation. Furthermore, 5FU treatment enhances the expression of the key RQC factors ZNF598 and GIGYF2 via an mTOR-dependent post-translational mechanism. This adaptation likely mitigates the cytotoxic consequences of increased ribosome collisions upon 5FU treatment.
PerturbAtlas: a comprehensive atlas of public genetic perturbation bulk RNA-seq datasets
Authors: Zhang Yiming , Zhang Ting , Yang Gaoxia , Pan Zhenzhong , Tang Min , Wen Yue , He Ping , Wang Yuan , Zhou Ran
Published: October 2024

Manipulating gene expression is crucial for understanding gene function, with high-throughput sequencing techniques such as RNA-seq elucidating the downstream mechanisms involved. However, the lack of a standardized metadata format for small-scale perturbation expression datasets in public repositories hinders their reuse. To address this issue, we developed PerturbAtlas, an add-value resource that re-analyzes publicly archived RNA-seq libraries to provide quantitative data on gene expression, transcript profiles, and alternative splicing events following genetic perturbation. PerturbAtlas assists users in identifying trends at the gene and isoform levels in perturbation assays by re-analyzing a curated set of 122 801 RNA-seq libraries across 13 species. This resource is freely available at https://perturbatlas.kratoss.site as both raw data tables and an interactive browser, allowing searches by species, tissue or genomic features. The results provide detailed information on alterations following perturbations, accessible through both forward and reverse approaches, thereby enabling the exploration of perturbation consequences and the identification of potential causal perturbations.
Trajectories of Adherence to Oral Pre-exposure Prophylaxis and Risks of HIV and Sexually Transmitted Infections
Authors: Unigwe Ikenna F , Goodin Amie , Lo-Ciganic Wei-Hsuan , Cook Robert L , Janelle Jennifer , Park Haesuk
Published: October 2024

Background

Pre-exposure prophylaxis (PrEP) effectiveness is highly dependent on medication adherence, which is associated with differential HIV risks and possibly sexually transmitted infection (STI).

Methods

This retrospective cohort study of PrEP users (01/01/2012–12/31/2021) used the MarketScan database of commercially insured enrollees to examine PrEP adherence trajectory groups’ associations with HIV and STI acquisition risks. Distinct PrEP adherence trajectories were identified by group-based trajectory modeling among individuals who used oral PrEP. The primary outcome was HIV acquisition incidence, and secondary was STI rate, compared among trajectory groups. Inverse probability treatment weighting time-varying Cox proportional hazards models assessed HIV acquisition, and Poisson regression models assessed STI.

Results

Among 23 258 oral PrEP users, 4 distinct PrEP adherence patterns were identified: minimal use (10.5% of the cohort), rapidly declining (25.4%), gradually declining (24.3%), and consistently high (39.8%). Compared with the minimal use group, the gradually declining (adjusted hazard ratio [AHR], 0.53; 95% CI, 0.31–0.90) and consistently high (AHR, 0.50; 95% CI, 0.30–0.84) PrEP adherence groups showed decreased HIV incidence risks. Compared with the minimal use group, the rapidly declining (adjusted incidence rate ratio [AIRR], 1.35; 95% CI, 1.07–1.72), gradually declining (AIRR, 1.73; 95% CI, 1.38–2.18), and consistently high (AIRR, 2.06; 95% CI, 1.64–2.58) groups were associated with increased STI risk.

Conclusions

These findings underscore the benefits of continuing and remaining adherent to PrEP and may also inform public health strategies, clinical guidelines, and interventions aimed at maximizing the effectiveness of PrEP in reducing new HIV infections while developing targeted strategies to prevent STIs with PrEP use.
Functional diversification of Sec13 isoforms for storage protein trafficking in rice endosperm cells
Authors: Wang Yongfei , Ren Yulong , Teng Xuan , Wang Fan , Chen Yanyu , Duan Erchao , Wang Xin , Pan Tian , Zhang Binglei , Wan Gexing , Zhang Yu , Zhang Pengcheng , Sun Xiejun , Yang Wenkun , Zhu Yun , Chen Yu , Zhao Wenjie , Han Xiaohang , Lei Cailin , Zhu Shanshan , Liu Shijia , Wang Yihua , Wan Jianmin
Published: October 2024

Coat protein complex II (COPII) vesicles play crucial roles in mediating the endoplasmic reticulum (ER) exit of newly synthesized proteins to the Golgi in eukaryotic cells. However, the molecular functions of COPII components and their functional diversifications in plant seeds remain obscure. Here, we showed that the rice (Oryza sativa) glutelin precursor accumulation12 (gpa12) mutant is defective in storage protein export from the ER, resulting in the formation of aggregated protein bodies. Map-based cloning revealed that GPA12 encodes a COPII outer layer protein, Sec13a, that mainly localizes to endoplasmic reticulum exit sites (ERES) and partially localizes to the Golgi. Biochemical experiments verified that Sec13a physically interacts with Sec31 and Sec16, and mutation in Sec13 compromises its interaction with Sec31 and Sec16, thereby affecting the membrane association of the inner complex components Sar1b and Sec23c. Apart from Sec13a, the rice genome encodes 2 other Sec13 isoforms, Sec13b and Sec13c. Notably, we observed an abnormal accumulation of globular ER structures in the sec13bc double mutant but not in the single mutants, suggesting a functional redundancy of Sec13b and Sec13c in modulating ER morphology. Taken together, our results substantiated that Sec13a plays an important role in regulating storage protein export from the ER, while Sec13b and Sec13c are required for maintaining ER morphology in rice endosperm cells. Our findings provide insights into the functional diversification of COPII components in plants.
Effectiveness and possible brain mechanisms of cervical invasive vagus nerve stimulation (iVNS) intervention for avoidant/restrictive food intake disorder: a case report
Authors: Cai Suping , Wang Yihan , Zhao Bofeng , Li Xiaoliang , He Huan , Yuan Kai , Zhao Qingchuan , Huang Qinxian , Yang Bin , Ji Gang
Published: October 2024

Background

We reported a case of cervical invasive vagus nerve stimulation (iVNS) treatment for avoidant/restrictive food intake disorder (ARFID) in a patient with severe anxiety and depression. This patient was even given a critical illness notice during his hospitalization and all treatment efforts were failed.

Objective

We aimed to verfiy the effectiveness of iVNS in a patient with ARFID.

Methods

We first attempted to perform cervical iVNS in this case and then observed the changes in clinical scores. We also analyzed the alterations in brain magnetic resonance imaging characteristics before and after iVNS using multi-modal neuroimagings.

Results

After 18 days of iVNS (from 1 to 19 July 2023), the patient's clinical symptoms improved significantly and he rapidly gained 5 kg in weight. The brain functional characteristics of this patient tended toward those of the normal group. Functional connectivities of the medial of orbitalis prefrontal cortex returned to the normal range after iVNS.

Conclusion

This is a precedent for performing cervical iVNS in an ARFID patient. Brain neural activity can be modulated through iVNS. The observed improvements in clinical scores and positive changes in brain function validated the effectiveness of iVNS. This case study provides evidence that this intervention technique could be used to reduce the burden on more similar ARFID patients.
Clinical case of 45,X/46,XY mosaic male with ejaculatory disorder associated with seminal vesicle dysplasia: a case report
Authors: Karibe Jurii , Takeshima Teppei , Takamoto Daiji , Kawahara Takashi , Osaka Kimito , Teranishi Jun-ichi , Makiyama Kazuhide , Uemura Hiroji , Yumura Yasushi
Published: October 2024

Introduction

45,X/46,XY mosaicism is a rare anomaly in sexual differentiation, presenting with diverse phenotypes and often leading to infertility due to abnormal gonadal development.

Aims

This report aims to present a case study of a 45,X/46,XY mosaic male patient with an ejaculatory disorder attributed to seminal vesicle dysplasia.

Methods

In this case study, diagnostic procedures encompassed blood tests, semen analysis, chromosomal examination, and imaging studies to assess gonadal morphology. Treatment strategies included attempted varicocelectomy, pharmacological intervention with amoxapine, and surgical testicular sperm extraction. Additionally, the patient underwent assisted reproductive techniques, specifically intracytoplasmic sperm injection (ICSI), to facilitate pregnancy for his wife.

Results

A 32-year-old man could not ejaculate, with post-orgasmic urinalysis revealing minimal sperm presence. Chromosomal analysis confirmed 45,X/46,XY mosaicism. Despite undergoing microsurgical varicocelectomy for clinical varicocele and receiving tricyclic antidepressants, no improvement in semen volume occurred. Imaging studies indicated ejaculatory disorder due to prostate and seminal vesicle aplasia. Consequently, surgical retrieval of testicular sperm was performed, leading to successful pregnancy via ICSI for his wife.

Conclusion

Our approach has effectively addressed ejaculatory disorder in 45,X/46,XY mosaic men, resulting in successful pregnancy.
Nectriaceae species associated to root rot of nursery and young Eucalyptus smithii trees in Uruguay with Ilyonectria charruensis as novel species
Authors: De Benedetti Franco , Carbone María Julia , Mondino Pedro , Alaniz Sandra
Published: October 2024

Forestry constitutes an important agronomical activity in Uruguay, involving the cultivation of exotic trees mainly for cellulose pulp production with Eucalyptus species. Over the last decade, E. smithii emerged as a species of interest for cellulose pulping. However, its rapid expansion has coincided with high mortality rates among young trees ranging from 5 to 85%, especially during the first and second summer after plantation. Disease surveys conducted on nine E. smithii commercial fields and three nurseries in southern and eastern Uruguay, yielded a collection of 25 isolates from E. smithii root rot belonging to the Nectriaceae family. In this study, we aimed to identify and characterize these isolates employing phenotypical and molecular studies and to assess their pathogenicity on E. smithii seedlings. Based on morphological features, the Nectriaceae isolates were subdivided into two groups, one resembling Calonectria (n=15) and another Cylindrocarpon-like (n=10). DNA sequences of the partial histone H3 (his3), actine, calmodulin, RNA polymerase II second largest subunit, translation elongation factor 1-alpha (tef1) and β-tubulin (tub2) genes were amplified for Calonectria, as well as partial his3, tef1, tub2 and internal-transcribed spacer and intervening 5.8S (ITS) for the Cylindrocarpon-like group. Based on phylogenetic analysis and phenotypical features three species were identified and characterized; Calonectria pauciramosa (n=15), Dactylonectria novozelandica (n=2), and a novel taxon which we describe here as Ilyonectria charruensis sp. nov. (n=8). The pathogenicity trials revealed that isolates from the three species significantly reduced both shoot and root dry weights of inoculated E. smithii seedlings compared to control plants.