bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of a distance-delivered mindfulness-based psychoeducation program on the psychological well-being, emotional intelligence and stress levels of nursing students in Turkey: a randomized controlled study
Authors: Öztürk Şenay
Published: October 2023

Nursing students who started university during the COVID-19 pandemic had to attend via distance education, which increased their stress. This study aimed to determine the effect of a mindfulness-based psychoeducation program on the psychological well-being, emotional intelligence and stress levels of young adults in their first year of an undergraduate nursing program at a university in Turkey. The sample consisted of 59 students (mean age 19.3 years) who were randomized to the intervention group (n = 29) and control group (n = 30). Those in the intervention group participated in a mindfulness-based psychoeducation program twice a week for 4 weeks via video conference. The Perceived Stress Scale (PSS-14), Psychological Well-Being Scale (PWB) and Revised Schutte Emotional Intelligence Scale (SEIS) were used as measurement tools. Between the pretest and posttest assessments, students in the intervention group showed a significant decrease in perceived stress scores and increases in emotional intelligence and psychological well-being scores. There were statistically significant differences in perceived stress, emotional intelligence and psychological well-being scores between the intervention and control groups in the posttest. Online mindfulness psychoeducation via video conferencing can be a useful intervention for nursing students to reduce stress and support psychological well-being and emotional intelligence.
Out-of-sample error estimation for M-estimators with convex penalty
Authors: Bellec Pierre C
Published: October 2023

A generic out-of-sample error estimate is proposed for $M$-estimators regularized with a convex penalty in high-dimensional linear regression where $(\boldsymbol{X},\boldsymbol{y})$ is observed and the dimension $p$ and sample size $n$ are of the same order. The out-of-sample error estimate enjoys a relative error of order $n^{-1/2}$ in a linear model with Gaussian covariates and independent noise, either non-asymptotically when $p/n\le \gamma $ or asymptotically in the high-dimensional asymptotic regime $p/n\to \gamma ^{\prime}\in (0,\infty )$. General differentiable loss functions $\rho $ are allowed provided that the derivative of the loss is 1-Lipschitz; this includes the least-squares loss as well as robust losses such as the Huber loss and its smoothed versions. The validity of the out-of-sample error estimate holds either under a strong convexity assumption, or for the L1-penalized Huber M-estimator and the Lasso under a sparsity assumption and a bound on the number of contaminated observations. For the square loss and in the absence of corruption in the response, the results additionally yield $n^{-1/2}$-consistent estimates of the noise variance and of the generalization error. This generalizes, to arbitrary convex penalty and arbitrary covariance, estimates that were previously known for the Lasso.
Nonmass Lesions on Breast US: An International Perspective on Clinical Use and Outcomes
Authors: Choi Ji Soo , Tsunoda Hiroko , Moon Woo Kyung
Published: October 2023

Nonmass lesions (NMLs) on breast US are defined as discrete areas of altered echotexture compared to surrounding breast tissue and lack the 3-dimensionality of a mass. They are not a component of American College of Radiology BI-RADS, but they are a finding type included in the Japan Association of Breast and Thyroid Sonology lexicon. Use of the NML finding is routine in many Asian practices, including the Samsung Medical Center and Seoul National University Hospital, and their features and outcomes have been investigated in multiple studies. Nonmass lesions are most often observed when US is used to evaluate mammographic asymmetries, suspicious calcifications, and nonmass enhancement on MRI and contrast-enhanced mammography. Nonmass lesions can be described by their echogenicity, distribution, presence or absence of associated calcifications, abnormal duct changes, architectural distortion, posterior shadowing, small cysts, and hypervascularity. Malignant lesions, especially ductal carcinoma in situ, can manifest as NMLs on US. There is considerable overlap between the US features of benign and malignant NMLs, and they also must be distinguished from normal variants. The literature indicates that NMLs with linear or segmental distribution, associated calcifications, abnormal duct changes, posterior shadowing, and hypervascularity are suggestive of malignancy, whereas NMLs with only interspersed small cysts are usually benign fibrocystic changes. In this article, we introduce the concepts of NMLs, illustrate US features suggestive of benign and malignant etiologies, and discuss our institutional approach for evaluating NMLs and an algorithm that we use to guide interpretation in clinical practice.
Protocol digest of a randomized controlled Phase III study comparing surgery alone versus adjuvant nivolumab versus adjuvant S-1 for locally advanced oesophageal squamous cell carcinoma with no pathological complete response after neoadjuvant chemotherapy followed by curative esophagectomy: Japan Clinical Oncology Group study JCOG2206 (SUNRISE Trial)
Authors: Kita Ryosuke , Matsuda Satoru , Nomura Motoo , Machida Ryunosuke , Sasaki Keita , Kato Ken , Goto Rei , Yoshioka Takashi , Yamamoto Shun , Tsushima Takahiro , Fukuda Haruhiko , Takeuchi Hiroya , Kitagawa Yuko ,   Japan Esophageal Oncology Group of the Japan Clinical Oncology Group
Published: October 2023

Although the efficacy of postoperative therapy with nivolumab after preoperative chemoradiotherapy for locally advanced oesophageal cancer has been proven in Western countries, the survival benefits of postoperative therapy after preoperative chemotherapy with docetaxel, cisplatin and 5-FU or cisplatin plus 5-FU as the Japanese standard therapy remain controversial. This randomized Phase III trial was designed to confirm the superiority of postoperative therapy with nivolumab over observation alone and S-1 over observation alone in patients with locally advanced oesophageal squamous cell carcinoma with no pathological complete response after preoperative chemotherapy followed by curative esophagectomy. A total of 450 patients will be enrolled from 56 hospitals in Japan over 5.5 years. The primary endpoint is relapse-free survival, and the secondary endpoints are disease-free survival, overall survival, adverse events and incremental cost-effectiveness ratio. This trial has been registered in the Japan Registry of Clinical Trials as jRCTs031230219 (https://jrct.niph.go.jp/latest-detail/jRCTs031230219).
Trend in overall survival from the start of first-line chemotherapy in patients with metastatic urothelial carcinoma
Authors: Yamamoto Shoma , Kato Minoru , Matsue Taisuke , Yukimatsu Nao , Takeyama Yuji , Otoshi Taiyo , Yamasaki Takeshi , Kuratsukuri Katsuyuki , Uchida Junji
Published: October 2023

New approaches involving immune checkpoint inhibitors and antibody-drug conjugates prolong overall survival in patients with metastatic urothelial carcinoma. However, the access to such systemic therapy in clinical practice is suboptimal, and whether these agents improve overall survival in patients with metastatic urothelial carcinoma over time remains unclear. Hence, we investigated the overall survival trend from the initiation of first-line therapy with these agents to identify changes due to the medication and time of treatment initiation. We retrospectively evaluated 195 patients from a single center. They were treated with chemotherapy, pembrolizumab, or avelumab or enfortumab vedotin. The treatment was categorized into chemotherapy, pembrolizumab or avelumab/enfortumab vedotin period. The new agents prolonged overall survival from the start of first-line therapy. Furthermore, sequential treatment with these agents in real-world clinical practice has been reported to prolong overall survival. These study results will have major implications when a new first-line therapy is approved in the future.
The Sociopolitical History of Sun-and-Sand Tourism in Mexico: Tourist Imaginaries and Resort Development from Acapulco to Cancún
Authors: Vitz Matthew
Published: October 2023

Histories of Mexico’s lucrative sun-and-sand tourism development have focused overwhelmingly on economic motivations and impacts, neglecting the political dimensions of how resorts were planned and how they were experienced by working-class residents. “The Sociopolitical History of Sun-and-Sand Tourism in Mexico” argues that the spatial planning of, and mid-century political contests over, Acapulco’s tourism economy, as well as rural political discontent in Guerrero and beyond, set the political and technical parameters within which Mexican officials planned resort destinations in the 1960s and 1970s. This article builds on recent scholarship that fuses political-economic and cultural approaches to examine the political culture of resort centers, wherein the actions of both elite and popular groups explain how resort development took place in Mexico. It tells the neglected political history of resort development in Mexico, beginning with the 1940s planning of Acapulco through the populist reforms of President Luis Echeverría (1970–1976).
Modelling the AM CVn and double detonation supernova progenitor binary system CD-30°11223
Authors: Deshmukh Kunal , Bauer Evan B , Kupfer Thomas , Dorsch Matti
Published: October 2023

We present a detailed modelling study of CD-30°11223 (CD-30), a hot subdwarf (sdB)-white dwarf (WD) binary identified as a double detonation supernova progenitor, using the open-source stellar evolution software MESA. We focus on implementing binary evolution models carefully tuned to match the observed characteristics of the system including log g and Teff. For the first time, we account for the structure of the hydrogen envelope throughout the modelling, and find that the inclusion of element diffusion is important for matching the observed radius and temperature. We investigate the two sdB mass solutions (0.47 and 0.54 M⊙) previously proposed for this system, strongly favouring the 0.47 M⊙ solution. The WD cooling age is compared against the sdB age using our models, which suggest an sdB likely older than the WD, contrary to the standard assumption for compact sdB-WD binaries. Subsequently, we propose a possible alternate formation channel for CD-30. We also perform binary evolution modelling of the system to study various aspects such as mass transfer, orbital period evolution, and luminosity evolution. Our models confirm CD-30 as a double detonation supernova progenitor, expected to explode ≈55 Myr from now. The WD accretes an ≈0.17 M⊙ thick helium shell that causes a detonation, leaving a 0.30 M⊙ sdB ejected at ≈750 km s−1. The final 15 Myr of the system are characterized by helium accretion which dominates the system luminosity, possibly resembling an AM CVn-type system.
Model-based characterization of the equilibrium dynamics of transcription initiation and promoter-proximal pausing in human cells
Authors: Zhao Yixin , Liu Lingjie , Hassett Rebecca , Siepel Adam
Published: October 2023

In metazoans, both transcription initiation and the escape of RNA polymerase (RNAP) from promoter-proximal pausing are key rate-limiting steps in gene expression. These processes play out at physically proximal sites on the DNA template and appear to influence one another through steric interactions. Here, we examine the dynamics of these processes using a combination of statistical modeling, simulation, and analysis of real nascent RNA sequencing data. We develop a simple probabilistic model that jointly describes the kinetics of transcription initiation, pause-escape, and elongation, and the generation of nascent RNA sequencing read counts under steady-state conditions. We then extend this initial model to allow for variability across cells in promoter-proximal pause site locations and steric hindrance of transcription initiation from paused RNAPs. In an extensive series of simulations, we show that this model enables accurate estimation of initiation and pause-escape rates. Furthermore, we show by simulation and analysis of real data that pause-escape is often strongly rate-limiting and that steric hindrance can dramatically reduce initiation rates. Our modeling framework is applicable to a variety of inference problems, and our software for estimation and simulation is freely available.
CasPEDIA Database: a functional classification system for class 2 CRISPR-Cas enzymes
Authors: Adler Benjamin A , Trinidad Marena I , Bellieny-Rabelo Daniel , Zhang Elaine , Karp Hannah M , Skopintsev Petr , Thornton Brittney W , Weissman Rachel F , Yoon Peter H , Chen LinXing , Hessler Tomas , Eggers Amy R , Colognori David , Boger Ron , Doherty Erin E , Tsuchida Connor A , Tran Ryan V , Hofman Laura , Shi Honglue , Wasko Kevin M , Zhou Zehan , Xia Chenglong , Al-Shimary Muntathar J , Patel Jaymin R , Thomas Vienna C J X , Pattali Rithu , Kan Matthew J , Vardapetyan Anna , Yang Alana , Lahiri Arushi , Maxwell Micaela F , Murdock Andrew G , Ramit Glenn C , Henderson Hope R , Calvert Roland W , Bamert Rebecca S , Knott Gavin J , Lapinaite Audrone , Pausch Patrick , Cofsky Joshua C , Sontheimer Erik J , Wiedenheft Blake , Fineran Peter C , Brouns Stan J J , Sashital Dipali G , Thomas Brian C , Brown Christopher T , Goltsman Daniela S A , Barrangou Rodolphe , Siksnys Virginius , Banfield Jillian F , Savage David F , Doudna Jennifer A
Published: October 2023

CRISPR-Cas enzymes enable RNA-guided bacterial immunity and are widely used for biotechnological applications including genome editing. In particular, the Class 2 CRISPR-associated enzymes (Cas9, Cas12 and Cas13 families), have been deployed for numerous research, clinical and agricultural applications. However, the immense genetic and biochemical diversity of these proteins in the public domain poses a barrier for researchers seeking to leverage their activities. We present CasPEDIA (http://caspedia.org), the Cas Protein Effector Database of Information and Assessment, a curated encyclopedia that integrates enzymatic classification for hundreds of different Cas enzymes across 27 phylogenetic groups spanning the Cas9, Cas12 and Cas13 families, as well as evolutionarily related IscB and TnpB proteins. All enzymes in CasPEDIA were annotated with a standard workflow based on their primary nuclease activity, target requirements and guide-RNA design constraints. Our functional classification scheme, CasID, is described alongside current phylogenetic classification, allowing users to search related orthologs by enzymatic function and sequence similarity. CasPEDIA is a comprehensive data portal that summarizes and contextualizes enzymatic properties of widely used Cas enzymes, equipping users with valuable resources to foster biotechnological development. CasPEDIA complements phylogenetic Cas nomenclature and enables researchers to leverage the multi-faceted nucleic-acid targeting rules of diverse Class 2 Cas enzymes.
GenBank 2024 Update
Authors: Sayers Eric W , Cavanaugh Mark , Clark Karen , Pruitt Kim D , Sherry Stephen T , Yankie Linda , Karsch-Mizrachi Ilene
Published: October 2023

GenBank® (https://www.ncbi.nlm.nih.gov/genbank/) is a comprehensive, public database that contains 25 trillion base pairs from over 3.7 billion nucleotide sequences for 557 000 formally described species. Daily data exchange with the European Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. Recent updates include policies for including spatio-temporal metadata, clarified documentation for GenBank data processing, enhanced foreign contamination screening tools, new processes in the Submission Portal, migration of Entrez Genome and Assembly displays into NCBI Datasets, and the impending retirement of tbl2asn, replaced by table2asn.
HumanLectome, an update of UniLectin for the annotation and prediction of human lectins
Authors: Schnider Boris , M’Rad Yacine , el Ahmadie Jalaa , de Brevern Alexandre G , Imberty Anne , Lisacek Frederique
Published: October 2023

The UniLectin portal (https://unilectin.unige.ch/) was designed in 2019 with the goal of centralising curated and predicted data on carbohydrate-binding proteins known as lectins. UniLectin is also intended as a support for the study of lectomes (full lectin set) of organisms or tissues. The present update describes the inclusion of several new modules and details the latest (https://unilectin.unige.ch/humanLectome/), covering our knowledge of the human lectome and comprising 215 unevenly characterised lectins, particularly in terms of structural information. Each HumanLectome entry is protein-centric and compiles evidence of carbohydrate recognition domain(s), specificity, 3D-structure, tissue-based expression and related genomic data. Other recent improvements regarding interoperability and accessibility are outlined.
LSM14B is essential for oocyte meiotic maturation by regulating maternal mRNA storage and clearance
Authors: Wan Yanling , Yang Shuang , Li Tongtong , Cai Yuling , Wu Xinyue , Zhang Mingyu , Muhammad Tahir , Huang Tao , Lv Yue , Chan Wai-Yee , Lu Gang , Li Jingxin , Sha Qian-Qian , Chen Zi-Jiang , Liu Hongbin
Published: October 2023

Fully grown oocytes remain transcriptionally quiescent, yet many maternal mRNAs are synthesized and retained in growing oocytes. We now know that maternal mRNAs are stored in a structure called the mitochondria-associated ribonucleoprotein domain (MARDO). However, the components and functions of MARDO remain elusive. Here, we found that LSM14B knockout prevents the proper storage and timely clearance of mRNAs (including Cyclin B1, Btg4 and other mRNAs that are translationally activated during meiotic maturation), specifically by disrupting MARDO assembly during oocyte growth and meiotic maturation. With decreased levels of storage and clearance, the LSM14B knockout oocytes failed to enter meiosis II, ultimately resulting in female infertility. Our results demonstrate the function of LSM14B in MARDO assembly, and couple the MARDO with mRNA clearance and oocyte meiotic maturation.
Public- and private-sector jobs: a cross-country perspective
Authors: Fenizia Alessandra , Checchi Daniele , Lucifora Claudio
Published: October 2023

This article reassesses the conventional wisdom that public-sector jobs have worse pay but better amenities than equivalent private-sector jobs, using data from 22 European countries and the USA. Earnings gaps are shown to be heterogeneous across countries—public sector work carries a premium in Europe but a penalty in the USA. However, whereas European public-sector workers report better job amenities—better job security and work–life balance—than their private-sector counterparts, there are no public–private amenity differentials for US workers. Public-sector work also has fewer pay-for-performance schemes. Finally, the public sector does not seem to ensure a fairer work environment, compared to the private sector, in terms of workplace discrimination and harassment. These stylized facts inform the external validity of extrapolating individual case studies to different contexts.
Clinical and Metagenomic Characterization of Neurological Infections of People With Human Immunodeficiency Virus in the Peruvian Amazon
Authors: Steinberg Hannah E , Ramachandran Prashanth S , Diestra Andrea , Pinchi Lynn , Ferradas Cusi , Kirwan Daniela E , Diaz Monica M , Sciaudone Michael , Wapniarski Annie , Zorn Kelsey C , Calderón Maritza , Cabrera Lilia , Pinedo-Cancino Viviana , Wilson Michael R , Asayag Cesar Ramal , Gilman Robert H , Bowman Natalie M ,   Toxoplasmosis Working Group in Peru, Apaza Catherine , Ayachi Melanie , Bocanegra Oliver A , Bok Jeroen , Pinedo Linda Chanamé , Urquizo Marilly Donayre , Gutierrez-Loli Renzo , Pinedo Gaston , Trompeter Grace , Vazquez Sory , Zhu Deanna
Published: October 2023

Background

Neurological opportunistic infections cause significant morbidity and mortality in people with human immunodeficiency virus (HIV) but are difficult to diagnose.

Methods

One hundred forty people with HIV with acute neurological symptoms from Iquitos, Peru, were evaluated for cerebral toxoplasmosis with quantitative polymerase chain reaction (qPCR) of cerebrospinal fluid (CSF) and for cryptococcal meningitis with cryptococcal antigen test (CrAg) in serum or CSF. Differences between groups were assessed with standard statistical methods. A subset of samples was evaluated by metagenomic next-generation sequencing (mNGS) of CSF to compare standard diagnostics and identify additional diagnoses.

Results

Twenty-seven participants were diagnosed with cerebral toxoplasmosis by qPCR and 13 with cryptococcal meningitis by CrAg. Compared to participants without cerebral toxoplasmosis, abnormal Glasgow Coma Scale score (P = .05), unilateral focal motor signs (P = .01), positive Babinski reflex (P = .01), and multiple lesions on head computed tomography (CT) (P = .002) were associated with cerebral toxoplasmosis. Photophobia (P = .03) and absence of lesions on head CT (P = .02) were associated with cryptococcal meningitis. mNGS of 42 samples identified 8 cases of cerebral toxoplasmosis, 7 cases of cryptococcal meningitis, 5 possible cases of tuberculous meningitis, and incidental detections of hepatitis B virus (n = 1) and pegivirus (n = 1). mNGS had a positive percentage agreement of 71% and a negative percentage agreement of 91% with qPCR for T gondii. mNGS had a sensitivity of 78% and specificity of 100% for Cryptococcus diagnosis.

Conclusions

An infection was diagnosed by any method in only 34% of participants, demonstrating the challenges of diagnosing neurological opportunistic infections in this population and highlighting the need for broader, more sensitive diagnostic tests for central nervous system infections.
Virologic Response to Dolutegravir Plus Lamivudine in People With Suppressed Human Immunodeficiency Virus Type 1 and Historical M184V/I: A Systematic Literature Review and Meta-analysis
Authors: Kabra Madhusudan , Barber Tristan J , Allavena Clotilde , Marcelin Anne-Geneviève , Di Giambenedetto Simona , Pasquau Juan , Gianotti Nicola , Llibre Josep M , Rial-Crestelo David , De Miguel-Buckley Rosa , Blick Gary , Turner Matthew , Harrison Cale , Wynne Tammy , Verdier Gustavo , Parry Chris M , Jones Bryn , Okoli Chinyere , Donovan Cynthia , Priest Julie , Letang Emilio
Published: October 2023

Background

To investigate the impact of the M184V/I mutation on virologic response to dolutegravir plus lamivudine (DTG + 3TC) in suppressed-switch populations, a meta-analysis was performed using virologic outcomes from people with human immunodeficiency virus type 1 (PWH) with and without M184V/I before DTG + 3TC switch in real-world studies identified via systematic literature review. Sensitivity analyses were performed using data from PWH with M184V/I in interventional studies identified via targeted literature review.

Methods

Single-arm meta-analyses using common- and random-effects models were used to estimate proportions of PWH with virologic failure (VF) among real-world populations with and without M184V/I and interventional study participants with M184V/I at 24, 48, and 96 weeks.

Results

Literature reviews identified 5 real-world studies from 3907 publications and 51 abstracts meeting inclusion criteria and 5 interventional studies from 1789 publications and 3 abstracts. All time points had low VF incidence in PWH with M184V/I (real-world: 1.43%–3.81%; interventional: 0.00%) and without (real-world: 0.73%–2.37%). Meta-analysis–estimated proportions (95% confidence interval) with VF were low at weeks 24, 48, and 96, respectively, for PWH with M184V/I (real-world: 0.01 [.00–.04], 0.03 [.01–.06], and 0.04 [.01–.07]; interventional: 0.00 [.00–.02], 0.00 [.00–.01], and 0.00 [.00–.03]) and without (real-world: 0.00 [.00–.02], 0.02 [.01–.04], and 0.02 [.00–.05]). One real-world study (n = 712) reported treatment-emergent M184V at VF in 1 of 652 (0.15%) PWH without prior M184V/I.

Conclusions

Results suggest that prior M184V/I has minimal impact on virologic suppression after switching to DTG + 3TC and provide reassurance when considering switching regimens in virologically suppressed PWH with incomplete treatment history or limited treatment options.
Seimei/KOOLS-IFU mapping of the gas and dust distributions in Galactic PNe: Unveiling the origin and evolution of the Galactic halo PN H4-1
Authors: Otsuka Masaaki , Ueta Toshiya , Tajitsu Akito
Published: October 2023

H4-1 is a planetary nebula (PN) located in the Galactic halo, and is notably carbon-rich and one of the most metal-deficient PNe in the Milky Way. To unveil its progenitor evolution through accurate measurement of the gas mass, we conducted a comprehensive investigation of H4-1, using the newly obtained Seimei/KOOLS-IFU spectra and multiwavelength spectro-photometry data. The emission-line images generated from the KOOLS-IFU data cube successfully resolve the ellipsoidal nebula and the equatorial flattened disk that are frequently seen in bipolar PNe evolved from massive progenitors. By a fully data-driven method, we directly derived the seven elemental abundances, the gas-to-dust mass ratio, and the gas and dust masses based on our own distance scale. By comparing the observed quantities with both the photoionization model and the binary nucleosynthesis model, we conclude that the progenitors of initial masses of 1.87 M$_{\odot }$ and 0.82 M$_{\odot }$ are second-generation stars formed ∼4 Gyr after the Big Bang that have undergone mass transfers and a binary merger, and have ultimately evolved into a PN showing unique chemical abundances. Our binary model successfully reproduces the observed abundances and also explains the evolutionary time scale of H4-1.
Neighboring inteins interfere with one another's homing capacity
Authors: Turgeman-Grott Israela , Arsenault Danielle , Yahav Dekel , Feng Yutian , Miezner Guy , Naki Doron , Peri Omri , Papke R Thane , Gogarten Johann Peter , Gophna Uri
Published: October 2023

Inteins are mobile genetic elements that invade conserved genes across all domains of life and viruses. In some instances, a single gene will have several intein insertion sites. In Haloarchaea, the minichromosome maintenance (MCM) protein at the core of replicative DNA helicase contains four intein insertion sites within close proximity, where two of these sites (MCM-a and MCM-d) are more likely to be invaded. A haloarchaeon that harbors both MCM-a and MCM-d inteins, Haloferax mediterranei, was studied in vivo to determine intein invasion dynamics and the interactions between neighboring inteins. Additionally, invasion frequencies and the conservation of insertion site sequences in 129 Haloferacales mcm homologs were analyzed to assess intein distribution across the order. We show that the inteins at MCM-a and MCM-d recognize and cleave their respective target sites and, in the event that only one empty intein invasion site is present, readily initiate homing (i.e. single homing). However, when two inteins are present co-homing into an intein-free target sequence is much less effective. The two inteins are more effective when invading alleles that already contain an intein at one of the two sites. Our in vivo and computational studies also support that having a proline in place of a serine as the first C-terminal extein residue of the MCM-d insertion site prevents successful intein splicing, but does not stop recognition of the insertion site by the intein's homing endonuclease.
Comprehensive assessment of sleep duration, insomnia, and brain structure within the UK Biobank cohort
Authors: Stolicyn Aleks , Lyall Laura M , Lyall Donald M , Høier Nikolaj Kjær , Adams Mark J , Shen Xueyi , Cole James H , McIntosh Andrew M , Whalley Heather C , Smith Daniel J
Published: October 2023

Study Objectives

To assess for associations between sleeping more than or less than recommended by the National Sleep Foundation (NSF), and self-reported insomnia, with brain structure.

Methods

Data from the UK Biobank cohort were analyzed (N between 9K and 32K, dependent on availability, aged 44 to 82 years). Sleep measures included self-reported adherence to NSF guidelines on sleep duration (sleeping between 7 and 9 hours per night), and self-reported difficulty falling or staying asleep (insomnia). Brain structural measures included global and regional cortical or subcortical morphometry (thickness, surface area, volume), global and tract-related white matter microstructure, brain age gap (difference between chronological age and age estimated from brain scan), and total volume of white matter lesions.

Results

Longer-than-recommended sleep duration was associated with lower overall grey and white matter volumes, lower global and regional cortical thickness and volume measures, higher brain age gap, higher volume of white matter lesions, higher mean diffusivity globally and in thalamic and association fibers, and lower volume of the hippocampus. Shorter-than-recommended sleep duration was related to higher global and cerebellar white matter volumes, lower global and regional cortical surface areas, and lower fractional anisotropy in projection fibers. Self-reported insomnia was associated with higher global gray and white matter volumes, and with higher volumes of the amygdala, hippocampus, and putamen.

Conclusions

Sleeping longer than recommended by the NSF is associated with a wide range of differences in brain structure, potentially indicative of poorer brain health. Sleeping less than recommended is distinctly associated with lower cortical surface areas. Future studies should assess the potential mechanisms of these differences and investigate long sleep duration as a putative marker of brain health.
Safety and pharmacokinetics of BI 685509, a soluble guanylyl cyclase activator, in patients with cirrhosis: A randomized Phase Ib study
Authors: Lawitz Eric J. , Reiberger Thomas , Schattenberg Jörn M. , Schoelch Corinna , Coxson Harvey O. , Wong Diane , Ertle Judith
Published: October 2023

Background:

Portal hypertension is a severe complication of cirrhosis. This Phase Ib study (NCT03842761) assessed the safety, tolerability, and pharmacokinetics of soluble guanylyl cyclase activator BI 685509 in patients with mild or moderate hepatic impairment (Child–Pugh [CP] A or B cirrhosis) and healthy volunteers (HVs).

Methods:

In this single-center, randomized, placebo-controlled study, patients received BI 685509 (maximum doses: 1, 2, or 3 mg, twice daily [BID]) or placebo for 28 days. HVs received one 0.5 mg dose of BI 685509 or placebo.

Results:

In total, 64 participants (CP-A, n=24; CP-B, n=25; HVs, n=15) were included; most commonly with NAFLD (36.7%), alcohol-associated (30.6%), or chronic viral hepatitis-related cirrhosis (28.6%). In patients with CP-A cirrhosis, drug-related adverse events (AEs) occurred in 5.6% of BI 685509-treated patients and 16.7% of placebo recipients. In patients with CP-B cirrhosis, drug-related AEs occurred in 26.3% of BI 685509-treated patients only. No serious AEs occurred in patients with CP-A cirrhosis; in patients with CP-B cirrhosis, serious AEs (not drug-related) occurred in 10.5% of BI 685509-treated patients and 16.7% of patients receiving placebo. BI 685509 was rapidly absorbed; exposure increased with dosage and was similar between etiologies and between patients with CP-A cirrhosis and patients with CP-A cirrhosis but lower in HVs. The mean percentage portal–systemic shunt fraction was measured in patients with CP-A cirrhosis and decreased at the end of treatment in the 2 mg BID (–11.2 ± 11.9%) and 3 mg BID (–14.0 ± 8.4%) BI 685509 dose groups, but not in the placebo group (+1.0 ± 27.3%).

Conclusion:

BI 685509 was generally well tolerated, with 3 serious, not drug-related AEs reported in patients with CP-B cirrhosis. In patients with CP-A cirrhosis, portal–systemic shunt fraction in the exploratory efficacy analysis was reduced by 2 mg BID and 3 mg BID BI 685509.
Inactivation of the paraventricular nucleus attenuates the cardiogenic sympathetic afferent reflex in the spontaneously hypertensive rat
Authors: Zahner Matthew R. , Brown Mary C. , Chandley Michelle J.
Published: October 2023

Background:

Myocardial ischemia causes the release of bradykinin, which stimulates cardiac afferents, causing sympathetic excitation and chest pain. Glutamatergic activation of the paraventricular hypothalamic nucleus (PVN) in the spontaneously hypertensive rat (SHR) drives elevated basal sympathetic activity. Thus, we tested the hypothesis that inactivation of the PVN attenuates the elevated reflex response to epicardial bradykinin in the SHR and that ionotropic PVN glutamate receptors mediate the elevated reflex.

Methods:

We recorded the arterial pressure and renal sympathetic nerve activity (RSNA) response to epicardial bradykinin application in anesthetized SHR and Wistar Kyoto (WKY) rats before and after PVN microinjection of GABAA agonist muscimol or ionotropic glutamate receptor antagonist kynurenic acid.

Results:

Muscimol significantly decreased the arterial pressure response to bradykinin from 180.4 ± 5.8 to 119.5 ± 6.9 mmHg in the SHR and from 111.8 ± 7.0 to 84.2 ± 8.3 mmHg in the WKY and the RSNA response from 186.2 ± 7.1 to 142.7 ± 7.3% of baseline in the SHR and from 201.0 ± 11.5 to 160.2 ± 9.3% of baseline in the WKY. Kynurenic acid significantly decreased the arterial pressure response in the SHR from 164.5 ± 5.0 to 126.2 ± 7.7 mmHg and the RSNA response from 189.9 ± 13.7to 168.5 ± 12.7% of baseline but had no effect in the WKY.

Conclusion:

These results suggest that tonic PVN activity is critical for the full manifestation of the CSAR in both the WKY and SHR. Glutamatergic PVN activity contributes to the augmented CSAR observed in the SHR.
Orthostatic hypotension, orthostatic hypertension, and ambulatory blood pressure in patients with chronic kidney disease in CRIC
Authors: Ghazi Lama , Cohen Jordana B. , Townsend Raymond R. , Drawz Paul E. , Rahman Mahboob , Pradhan Nishigandha , Cohen Debbie L. , Weir Matthew R. , Rincon-Choles Hernan , Juraschek Stephen P.
Published: October 2023

Background:

Orthostatic changes in blood pressure (BP), either orthostatic hypotension or orthostatic hypertension (OHTN), are common among patients with chronic kidney disease. Whether they are associated with unique out-of-office BP phenotypes is unknown.

Methods:

CRIC is a prospective, multicenter, observational cohort study of participants with CKD. BP measured at 2 min after standing and ambulatory BP monitoring (ABPM) were obtained on 1386 participants. Orthostatic hypotension was defined as a 20 mmHg drop in SBP or 10 mmHg drop in DBP when changing from seated to standing positions. Systolic and diastolic night-to-day ratio was also calculated. OHTN was defined as a 20 or 10 mmHg rise in SBP or DBP when changing from a seated to a standing position. White-coat effect (WCE) was defined as seated minus daytime ambulatory BP.

Results:

Of the 1386 participants (age: 58 ± 10 years, 44% female, 39% black), 68 had orthostatic hypotension and 153 had OHTN. Postural reduction in SBP or DBP was positively associated with greater systolic and diastolic WCE and systolic and diastolic night-to-day ratio. Orthostatic hypotension was positively associated with diastolic WCE (β = 3 [0.2, 5.9]). Diastolic OHTN was negatively associated with systolic WCE (β = -4 [-7.2, -0.5]) and diastolic WCE (β = -6 [-8.1, -4.2]).

Conclusion:

Postural change in BP was associated with WCE and night-to-day-ratio. Orthostatic hypotension was positively associated with WCE and OHTN was negatively associated with WCE. These findings strengthen observations that postural changes in BP may associate with distinct BP patterns throughout the day. These observations are informative for subsequent research tailoring orthostatic hypotension and OHTN treatment to specific BP phenotypes.
Single-cell RNA Sequencing Reveals Novel Cellular Factors for Response to Immunosuppressive Therapy in Aplastic Anemia
Authors: Jang Jinho , Kim Hongtae , Park Sung-Soo , Kim Miok , Min Yong Ki , Jeong Hyoung-oh , Kim Seunghoon , Hwang Taejoo , Choi David Whee-Young , Kim Hee-Je , Song Sukgil , Kim Dong Oh , Lee Semin , Lee Chang Hoon , Lee Jong Wook
Published: October 2023

Aplastic anemia (AA) is a lethal hematological disorder; however, its pathogenesis is not fully understood. Although immunosuppressive therapy (IST) is a major treatment option for AA, one-third of patients do not respond to IST and its resistance mechanism remains elusive. To understand AA pathogenesis and IST resistance, we performed single-cell RNA sequencing (scRNA-seq) of bone marrow (BM) from healthy controls and patients with AA at diagnosis. We found that CD34+ early-stage erythroid precursor cells and PROM1+ hematopoietic stem cells were significantly depleted in AA, which suggests that the depletion of CD34+ early-stage erythroid precursor cells and PROM1+ hematopoietic stem cells might be one of the major mechanisms for AA pathogenesis related with BM-cell hypoplasia. More importantly, we observed the significant enrichment of CD8+ T cells and T cell–activating intercellular interactions in IST responders, indicating the association between the expansion and activation of T cells and the positive response of IST in AA. Taken together, our findings represent a valuable resource offering novel insights into the cellular heterogeneity in the BM of AA and reveal potential biomarkers for IST, building the foundation for future precision therapies in AA.
Visual outcomes and risk factors of uveitis cataract eyes after phacoemulsification and manual small-incision cataract surgery
Authors: Shekhar Madhu , Chaudhary Sushmita , Pai Aruna , Rajesh Vedhanayaki , Balakrishnan Logesh , Nagu Kamatchi , Wijesinghe Hiruni Kaushalya
Published: October 2023

Purpose:

To examine the visual outcomes and risk factors of uveitis cataract eyes after phacoemulsification and manual small-incision cataract surgery (MSICS).

Setting:

Tertiary-care eye hospital in southern India.

Design:

Retrospective interventional case series.

Methods:

Of the uveitis eyes operated for cataract surgery between 2017 and 2020, eyes with a minimum of 6 months postoperative follow-up were included. Eyes with ocular trauma, lens subluxation, lens-induced uveitis, or retinal detachment–induced uveitis were excluded. Demography, visual acuity, intraoperative and postoperative records, and surgical outcomes were analyzed.

Results:

191 eyes of 191 patients with a mean age of 51.7 ± 14.4 years were included. Phacoemulsification was performed in 134 eyes, and 57 eyes underwent MSICS. Synechiolysis and pupil-expanding maneuvers were required in 74 eyes (38.7%). No differences were noted in the rates of complications between phacoemulsification and MSICS eyes, except at 1 year, where higher rates of posterior capsular opacification and vitritis were noted in MSICS eyes (P = .018). The visual outcomes of eyes that underwent MSICS and phacoemulsification were comparable (P = .463). In 12 eyes (13.5%), improvement in vision was not significant.

Conclusions:

This study shows phacoemulsification may be a preferred technique in uveitis cataracts, given the lesser incidence of postoperative complications. Patients should be counseled for realistic expectations.
The effect of experimental emotion induction on experimental pain: a systematic review and meta-analysis
Authors: Mikkelsen Mai Bjørnskov , Neumann Henrike , Buskbjerg Cecilie Rask , Johannsen Maja , O'Toole Mia Skytte , Arendt-Nielsen Lars , Zachariae Robert
Published: October 2023

The idea that emotions can influence pain is generally recognized. However, a synthesis of the numerous individual experimental studies on this subject is lacking. The aim of the present systematic review and meta-analysis was to synthesize the existing evidence on the effect of experimental emotion induction on experimental pain in nonclinical adults. PsycInfo and PubMed were searched up until April 10, 2023, for studies assessing differences in self-reported pain between emotion induction groups and/or control groups or between conditions within group. Risk of bias was assessed for the individual studies. The literature search yielded 78 relevant records of 71 independent studies. When compared with control conditions, the pooled results revealed a statistically significant pain-attenuating effect of positive emotion induction (between-group: Hedges g = −0.48, 95% CI: −0.72; −0.25, K = 9; within-group: g = −0.24, 95% CI: −0.32; −0.15, K = 40), and a statistically significant pain-exacerbating effect of negative emotion induction in within-group analyses but not between-group analyses (between-group: g = −0.29, 95% CI: −0.66; 0.07, K = 10; within-group: g = 0.14, 95% CI: 0.06; 0.23, K = 39). Bayesian meta-analysis provided strong support for an effect of positive emotion induction but weak support for an effect of negative emotion induction. Taken together, the findings indicate a pain-attenuating effect of positive emotion induction, while the findings for negative emotion induction are less clear. The findings are discussed with reference to theoretical work emphasizing the role of motivational systems and distraction for pain. Limitations include considerable heterogeneity across studies limiting the generalizability of the findings.
Deactivation of dorsal CA1 pyramidal neurons projecting to medial prefrontal cortex contributes to neuropathic pain and short-term memory impairment
Authors: Han Shuang , Ren Jiale , Li Ziming , Wen Junjian , Jiang Bin , Wei Xuhong
Published: October 2023

Neuropathic pain after peripheral nerve injury is a multidimensional experience that includes sensory, affective, and cognitive components that interact with one another. Hypoexcitation of the medial prefrontal cortex (mPFC) was observed in mice with peripheral nerve injury, but the changes in neural inputs onto the mPFC have not been completely explored. Here, we report that the neural terminals from the dorsal hippocampus CA1 (dCA1) form excitatory connection with layer 5 pyramidal neurons in the prelimbic area (PrL) of the mPFC. Spared nerve injury (SNI) induced a reduction in the intrinsic excitability of dCA1 pyramidal neurons innervating the PrL and impairment in excitatory synaptic transmission onto dCA1 pyramidal cells. Specifically, activating the neural circuit from dCA1 to mPFC alleviated neuropathic pain behaviors and improved novel object recognition ability in SNI mice, whereas deactivating this pathway in naïve animals recapitulated tactile allodynia and memory deficits. These results indicated that hypoactivity in dCA1 pyramidal cells after SNI in turn deactivated layer 5 pyramidal neurons in PrL and ultimately caused pain hypersensitivity and memory deficits.
A Multicenter Comparison of 1-yr Functional Outcomes and Programming Differences Between the Advanced Bionics Mid-Scala and SlimJ Electrode Arrays
Authors: Eitutis Susan T. , Vickers Deborah A. , Tebbutt Karen , Thomas Tisa , Jiang Dan , de Klerk Anel , Clemesha Jennifer , Chung Mark , Bance Manohar L.
Published: October 2023

Objective

To determine if there is a difference in hearing outcomes or stimulation levels between Advanced Bionics straight and precurved arrays.

Study design

Retrospective chart review across three implant centers.

Setting

Tertiary centers for cochlear and auditory brainstem implantation.

Patients

One hundred fifteen pediatric and 205 adult cochlear implants (CIs) were reviewed. All patients were implanted under the National Institute for Health and Care Excellence 2009 guidelines with a HiRes Ultra SlimJ or Mid-Scala electrode array.

Main outcome measures

Hearing preservation after implantation, as well as CI-only listening scores for Bamford-Kowal-Bench sentences were compared 1 year after implantation. Stimulation levels for threshold and comfort levels were also compared 1 year after implantation.

Results

Hearing preservation was significantly better with the SlimJ compared with the Mid-Scala electrode array. Bamford-Kowal-Bench outcomes were not significantly different between the two arrays in any listening condition. Stimulation levels were not different between arrays but did vary across electrode contacts. At least one electrode was deactivated in 33% of implants but was more common for the SlimJ device.

Conclusion

Modern straight and precurved arrays from Advanced Bionics did not differ in hearing performance or current requirements. Although hearing preservation was possible with both devices, the SlimJ array would still be the preferred electrode in cases where hearing preservation was a priority. Unfortunately, the SlimJ device was also prone to poor sound perception on basal electrodes. Further investigation is needed to determine if deactivated electrodes are associated with electrode position/migration, and if programming changes are needed to optimize the use of these high-frequency channels.
Navigation systems and 3D imaging in percutaneous nephrolithotripsy: improving outcomes and safety
Authors: Bouchalakis Athanasios , Somani Bhaskar Kumar , Lima Estevao , Rassweiler-Seyfried Marie-Claire , Mamoulakis Charalampos , Tokas Theodoros
Published: October 2023

Purpose of review

Percutaneous nephrolithotripsy (PCNL) is the first-line management option for large kidney stones (>2 cm). It remains, however, a demanding procedure with considerable morbidity. The present narrative review summarizes recent knowledge from original research studies investigating navigation systems/three-dimensional (3D) imaging in PCNL, particularly on publications during the past 12–18 months.

Recent findings

Navigation systems and 3D imaging are primarily used for preoperative planning, with few intra-operative applications. Patient management and residents’ training could benefit from their use.

Navigation systems and 3D imaging technology have emerged as a potential game-changer in PCNL. Even though available evidence is currently scarce/inconclusive, the safety/efficacy of navigation systems and 3D dimensional imaging use in PCNL appears promising. This advanced technology offers precise anatomical mapping, improved visualization, and surgical accuracy. Enabling a comprehensive preoperative evaluation and improving guidance, navigation systems, and 3D imaging technology may improve the safety and efficacy of PCNL. With continuous technological evolution, it is expected that improvements/innovations will offer further aid in such demanding procedures. Familiarization and cost reduction are necessary for widespread application, while larger-scale prospective studies and well designed randomized controlled trials are still needed.