bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive Landscape of Non-muscle Invasive Bladder Cancer Tumour Microenvironment and Prognostic value of Cancer-Associated Myofibroblasts
Authors: Cañizo Carmen G. , Guerrero-Ramos Félix , Escavy Mercedes Perez , Lodewijk Iris , Suárez-Cabrera Cristian , Morales Lucía , Nunes Sandra P , Munera-Maravilla Ester , Rubio Carolina , Sánchez Rebeca , Rodriguez-Izquierdo Marta , Martínez de Villarreal Jaime , Real Francisco X. , Castellano Daniel , Martín-Arriscado Cristina , Pablos David Lora , Antolín Alfredo Rodríguez , Dueñas Marta , Paramio Jesús M. , Martínez Victor G.
Published: October 2023

BACKGROUND

Non-muscle-invasive bladder cancer (NMIBC) poses clinical challenges due to its high recurrence and progression rates. While Bacillus Calmette-Guérin (BCG) remains as the gold standard treatment for high-risk NMIBC, recent irruption of anti-PD-1/PD-L1 drugs claims for a comprehensive understanding of the tumour microenvironment (TME) of these tumors.

METHODS

The present prospective study consisted on the analysis 98 fresh NMIBC samples, tumor and non-pathological tissue, via flow cytometry. Final analysis included distribution of 11 cell types and the expression of PD-L1 in 66 tumor and 62 non-pathological tissue biopsies from 73 NMIBC patients (84.4% paired samples). The results were validated using publicly available transcriptomic data, and histology.

RESULTS

In comparison to non-pathological tissue, the TME of NMIBC presented microvascular alterations, increased cancer-associated fibroblast (CAF) and myofibroblast (myoCAF) presence, and varied immune cell distribution. Heterogeneous PD-L1 expression was observed across subsets, with cancer cells as primary potential anti-PD-L1 binding targets. Unbiased analysis revealed that myoCAF and M2-like macrophages are enriched in high grade NMIBC tumors, but only myoCAF were associated with higher rates of progression and recurrence, as we confirmed in three independent transcriptomic cohorts (888 total patients). We further validated the prognostic value of myoCAFs by tissue micro-array.

CONCLUSION

This comprehensive analysis provides a roadmap to establish the full landscape of the NMIBĆs TME, highlighting myoCAFs as potential prognostic markers.

FUNDING

This study was funded by FC AECC (INVES222946GARC), Consejería de Educación, Ciencia y Universidades de la CAM (2018-T2/BMD-10342), Hoffmann-La Roche, Ministerio de Ciencia e Innovación (INMUNOEPIBLA) and ISCIII/FEDER (CIBERONC CB16/12/00489)
Ubiquitous purine sensor modulates diverse signal transduction pathways in bacteria
Authors: Monteagudo-Cascales Elizabet , Gumerov Vadim M. , Fernández Matilde , Matilla Miguel A. , Gavira José A. , Zhulin Igor B. , Krell Tino
Published: October 2023

Purines and their derivatives are key molecules for controlling intracellular energy homeostasis and nucleotide synthesis. In eukaryotes, including humans, purines also act as signaling molecules that mediate extracellular communication and control key cellular processes, such as proliferation, migration, differentiation, and apoptosis. However, the signaling role of purines in bacteria is largely unknown. Here, by combining structural and sequence information, we define a purine-binding motif, which is present in sensor domains of thousands of bacterial receptors that modulate motility, gene expression, metabolism and second messenger turnover. The screening of compound libraries and microcalorimetric titrations of selected sensor domains validated their ability to specifically bind purine derivatives. The physiological relevance of purine sensing was demonstrated in a second messenger signaling system that modulates c-di-GMP levels.
Regulation of NRF2 by Phosphoinositides and Small Heat Shock Proteins
Authors: Chen Changliang , Chen Mo , Wen Tianmu , Awasthi Poorwa , Carrillo Noah D. , Anderson Richard A. , Cryns Vincent L.
Published: October 2023

Reactive oxygen species (ROS) are generated by aerobic metabolism, and their deleterious effects are buffered by the cellular antioxidant response, which prevents oxidative stress. The nuclear factor erythroid 2-related factor 2 (NRF2) is a master transcriptional regulator of the antioxidant response. Basal levels of NRF2 are kept low by ubiquitin-dependent degradation of NRF2 by E3 ligases, including the Kelch-like ECH-associated protein 1 (KEAP1). Here, we show that the stability and function of NRF2 is regulated by the type I phosphatidylinositol phosphate kinase γ (PIPKIγ), which binds NRF2 and transfers its product phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) to NRF2. PtdIns(4,5)P2binding recruits the small heat shock protein HSP27 to the complex. Silencing PIPKIγ or HSP27 destabilizes NRF2, reduces expression of its target gene HO-1, and sensitizes cells to oxidative stress. These data demonstrate an unexpected role of phosphoinositides and HSP27 in regulating NRF2 and point to PIPKIγ and HSP27 as drug targets to destabilize NRF2 in cancer.

In brief

Phosphoinositides are coupled to NRF2 by PIPKIγ, and HSP27 is recruited and stabilizes NRF2, promoting stress-resistance.
Senescence of endplate osteoclasts induces sensory innervation and spinal pain
Authors: Pan Dayu , Benkato Kheiria Gamal , Han Xuequan , Zheng Jinjian , Kumar Vijay , Wan Mei , Zheng Junying , Cao Xu
Published: October 2023

Spinal pain affects individuals of all ages and is the most common musculoskeletal problem globally. Its clinical management remains a challenge as the underlying mechanisms leading to it are still unclear. Here, we report that significantly increased numbers of senescent osteoclasts (SnOCs) are observed in mouse models of spinal hypersensitivity, like lumbar spine instability (LSI) or aging, compared to controls. The larger population of SnOCs is associated with induced sensory nerve innervation, as well as the growth of H-type vessels, in the porous endplate. We show that deletion of senescent cells by administration of the senolytic drug Navitoclax (ABT263) results in significantly less spinal hypersensitivity, spinal degeneration, porosity of the endplate, sensory nerve innervation and H-type vessel growth in the endplate. We also show that there is significantly increased SnOC-mediated secretion of Netrin-1 and NGF, two well-established sensory nerve growth factors, compared to non-senescent OCs. These findings suggest that pharmacological elimination of SnOCs may be a potent therapy to treat spinal pain.
Analytical method for reconstructing the stress on a spherical particle from its surface deformation
Authors: Krüger Lea Johanna , te Vrugt Michael , Bröker Stephan , Wallmeyer Bernhard , Betz Timo , Wittkowski Raphael
Published: October 2023

The mechanical forces that cells experience from the tissue surrounding them are crucial for their behavior and development. Experimental studies of such mechanical forces require a method for measuring them. A widely used approach in this context is bead deformation analysis, where spherical particles are embedded into the tissue. The deformation of the particles then allows to reconstruct the mechanical stress acting on them. Existing approaches for this reconstruction are either very time-consuming or not sufficiently general. In this article, we present an analytical approach to this problem based on an expansion in solid spherical harmonics that allows us to find the complete stress tensor describing the stress acting on the tissue. Our approach is based on the linear theory of elasticity and uses an ansatz derived by Love. We clarify the conditions under which this ansatz can be used, making our results useful also for other contexts in which this ansatz is employed. Our method can be applied to arbitrary radial particle deformations and requires a very low computational effort. The usefulness of the method is demonstrated by an application to experimental data.

STATEMENT OF SIGNIFICANCE

Measurements of mechanical forces acting on cells in a tissue are important for understanding the physical behavior of biological systems, but they are also quite challenging. A common strategy is to place a spherical bead inside the tissue and to then reconstruct the mechanical stress from the bead deformation that this stress causes. Here, we introduce a novel analytical method using which this reconstruction can be achieved. This method is significantly faster than numerical approaches and significantly more general than existing analytical techniques, such that it can be expected to find a broad range of applications in mechanobiology.
Impact of Memory T Cells on SARS-COV-2 Vaccine Response in Hematopoietic Stem Cell Transplant
Authors: VanOudenhove Jennifer , Liu Yuxin , Nelakanti Raman , Kim Dongjoo , Busarello Emma , Ovalle Natalia Tijaro , Qi Zhihong , Mamillapalli Padmavathi , Siddon Alexa , Bai Zhiliang , Axtmayer Alfredo , Corso Cheryl , Kothari Shalin , Foss Francine , Isufi Iris , Tebaldi Toma , Gowda Lohith , Fan Rong , Seropian Stuart , Halene Stephanie
Published: October 2023

During the COVID-19 pandemic, hematopoietic stem cell transplant (HSCT) recipients faced an elevated mortality rate from SARS-CoV-2 infection, ranging between 10-40%. The SARS-CoV-2 mRNA vaccines are important tools in preventing severe disease, yet their efficacy in the post-transplant setting remains unclear, especially in patients subjected to myeloablative chemotherapy and immunosuppression. We evaluated the humoral and adaptive immune responses to the SARS-CoV-2 mRNA vaccination series in 42 HSCT recipients and 5 healthy controls. Peripheral blood mononuclear nuclear cells and serum were prospectively collected before and after each dose of the SARS-CoV-2 vaccine. Post-vaccination responses were assessed by measuring anti-spike IgG and nucleocapsid titers, and antigen specific T cell activity, before and after vaccination. In order to examine mechanisms behind a lack of response, pre-and post-vaccine samples were selected based on humoral and cellular responses for single-cell RNA sequencing with TCR and BCR sequencing. Our observations revealed that while all participants eventually mounted a humoral response, transplant recipients had defects in memory T cell populations that were associated with an absence of T cell response, some of which could be detected pre-vaccination.
How Much Does TRPV1 Deviate from An Ideal MWC-Type Protein
Authors: Li Shisheng , Zheng Jie
Published: October 2023

Many ion channels are known to behave as an allosteric protein, coupling environmental stimuli captured by specialized sensing domains to the opening of a central pore. The classic Monod-Wyman-Changeux (MWC) model, originally proposed to describe binding of gas molecules to hemoglobin, has been widely used for analyzing ion channel gating. Here we address the issue of how accurate the MWC model predicts activation of the capsaicin receptor TRPV1 by vanilloids. Taking advantage of a concatemeric design that makes it possible to lock TRPV1 in states with zero-to-four bound vanilloid molecules, we showed quantitatively that the overall gating behavior is satisfactorily predicted by the MWC model. There is however a small yet detectable subunit position effect: ligand binding to two kitty-corner subunits is 0.4-to-0.6 kcal/mol more effective in inducing opening than binding to two neighbor subunits. This difference, less than 10% of the overall energetic contribution from ligand binding, is not expected in hemoglobin, in which each subunit is related equivalently to all the other subunits.

Significance

The MWC model, proposed more than 50 years ago, is elegantly simple yet powerful in predicting the behavior of allosteric proteins like hemoglobin. Its prediction power for ion channel gating has been beautifully demonstrated in the studies of BK channels. Our present work aims to determine how accurate the MWC model predicts TRPV1 activation induced by vanilloids. Our findings support the notion that the evolutionary drive upon allosteric proteins applies generally to multi-subunit proteins.
Health impact and cost-effectiveness of expanding routine immunization coverage in India through Intensified Mission Indradhanush: a quasi-experimental study and economic evaluation
Authors: Clarke-Deelder Emma , Suharlim Christian , Chatterjee Susmita , Portnoy Allison , Brenzel Logan , Ray Arindam , Cohen Jessica , Menzies Nicolas A , Resch Stephen C
Published: October 2023

Background

Many children do not receive a full schedule of childhood vaccines, yet there is limited evidence on the cost-effectiveness of strategies for improving vaccination coverage. We evaluated the cost-effectiveness of periodic intensification of routine immunization (PIRI), a widely applied strategy for increasing vaccination coverage.

Methods

Intensified Mission Indradhanush (IMI) was a large-scale PIRI intervention implemented in India in 2017–2018. In 40 sampled districts, we measured the incremental economic cost of IMI using primary data, and used a quasi-experimental impact evaluation to estimate incremental vaccination doses delivered. We estimated deaths and disability-adjusted life years (DALYs) averted using the Lives Saved Tool and reported cost-effectiveness from government provider and societal perspectives.

Findings

In sampled districts, IMI had an estimated incremental cost of 2021US$15.7 (95% uncertainty interval: 11.9 to 20.1) million from a provider perspective and increased vaccine delivery by an estimated 2.2 (−0.5 to 4.8) million doses, averting an estimated 1,413 (−350 to 3,129) deaths. The incremental cost was $7.14 per dose ($3.20 to dominated), $95.24 per zero-dose child reached ($45.48 to dominated), $375.98 ($168.54 to dominated) per DALY averted, $413.96 ($185.56 to dominated) per life-year saved, and $11,133 ($4,990 to dominated) per under-five death averted. At a cost-effectiveness threshold of 1x per-capita GDP per DALY averted, IMI was estimated to be cost-effective with 89% probability.

Interpretation

This evidence suggests IMI was both impactful and cost-effective for improving vaccination coverage. As vaccination programs expand coverage, unit costs may increase due to the higher costs of reaching currently unvaccinated children.

Funding

Bill & Melinda Gates Foundation
Movement-related drivers of exposure to West Nile virus by American robins (Turdus migratorius)
Authors: Jahn Alex E. , Koller Kyle , Martin Lynn B. , Smiley Tara M. , Verrett Taylor B. , Ketterson Ellen D. , Williams Emily J. , Becker Daniel J.
Published: October 2023

The ecological processes that determine how individual animals become hosts to zoonotic pathogens is a topic of rapidly growing interest. However, how such exposure is mediated by context (e.g., season, location), host behavior (e.g., migration distance) and host demographics is generally poorly understood. We evaluated seasonal exposure to West Nile Virus of American robins sampled in Indiana and compared our results to those of previous studies. Because robins that breed in Indiana are partial migrants (i.e., only a portion of the population migrates), we evaluated their probability of exposure to WNV as a function of whether they migrated or not and of their movement distance. We also tagged a subset of breeding robins with tracking devices to evaluate their potential to disperse the virus between Indiana and other regions of the continent. We found that robins that breed in Indiana are exposed to WNV at a higher rate than that detected in previous studies, but found no correlation between robin exposure and whether a robin migrated or not, nor with migration distance, season, sex, and breeding latitude (for robins overwintering in Indiana). Our tracking data indicate that robins that breed in Indiana migrate several hundred miles to overwinter in the southeastern US. The mean duration of their return to Indiana in spring is 10.3 days, which is less than the maximum infectious period found for robins in previous studies, suggesting that they have the capacity to move WNV long distances in spring. However, we still know little about the physiological capacity of robins to migrate while being infectious, which could inhibit the dispersal of the virus through robin migration. Future research on the physiological, ecological and behavioral factors mediating the exposure of birds to WNV will lend insight into the role that robins and other birds play in the transmission ecology of the virus.
Dynamic layer-specific processing in the prefrontal cortex during working memory
Authors: Degutis Jonas Karolis , Chaimow Denis , Haenelt Daniel , Assem Moataz , Duncan John , Haynes John-Dylan , Weiskopf Nikolaus , Lorenz Romy
Published: October 2023

The dorsolateral prefrontal cortex (dlPFC) is reliably engaged in working memory (WM). Evidence from non-human primates indicates that the dlPFC comprises different cytoarchitectonic layers that play distinct roles in WM subprocesses; yet the functional role of the dlPFC’s laminar circuitry in human WM is not well understood. In this study, participants completed a delayed-match-to-sample WM task while undergoing functional magnetic resonance imaging (fMRI) at ultra-high resolution, which allowed us to examine layer-specific responses of the dlPFC to manipulations in WM load and motor response. We conducted univariate and multivariate analyses across all periods of the WM task: encoding, delay and retrieval. First, we observed that superficial layers activate stronger than deep layers to higher WM load during the delay period. This aligns with earlier work showing preferential superficial layer activation to WM manipulation and as such may indicate lamina-specific activation of the frontoparietal network to heightened task demands more generally. Second, we found that superficial layers show higher decoding of WM load differences than deep layers during the retrieval period. In this context, we could show that decoding of WM load in the superficial layer exhibited dynamic changes across the encoding, delay and retrieval period of the task, indicative of separate WM control processes that occur on the WM content. Last, we found that superficial and deep layers are both non-differentially involved in the motor response, contradicting earlier findings of a preferential deep layer activation in humans. Taken together, our results provide new insights into the functional laminar circuitry of the dlPFC during WM and provide further support for a dynamic account of dlPFC coding.
WOX11-mediated cell size control in Arabidopsis attenuates fecundity of endoparasitic cyst nematodes
Authors: Guarneri Nina , Willig Jaap-Jan , Willemsen Viola , Goverse Aska , Sterken Mark G. , Nibbering Pieter , Lozano-Torres Jose L. , Smant Geert
Published: October 2023

Cyst nematodes establish permanent feeding structures called syncytia inside host root vasculature, disrupting the flow of water and minerals. In response, plants form WOX11-mediated adventitious lateral roots at nematode infection sites. WOX11-adventitious lateral rooting modulates tolerance to nematode infections, however, whether this also benefits nematode parasitism remains unknown.

Here, we report on bioassays using a35S::WOX11-SRDXtranscriptional repressor mutant to investigate whether WOX11-adventitious lateral rooting promotes syncytium development and thereby female fecundity. Moreover, we chemically inhibited cellulose biosynthesis to verify if WOX11 directly modulates cell wall plasticity in syncytia. Finally, we performed histochemical analyses to test if WOX11 mediates syncytial cell wall plasticity via reactive oxygen species (ROS).

Repression of WOX11-mediated transcription specifically enhanced the radial expansion of syncytial elements, increasing both syncytium size and female offspring. The enhanced syncytial hypertrophy observed in the35S::WOX11-SRDXmutant could be phenocopied by chemical inhibition of cellulose biosynthesis and was associated with elevated levels of ROS at nematode infection sites.

We therefore conclude that WOX11 restricts radial expansion of nematode feeding structures and female fecundity, likely by modulating ROS-mediated cell wall plasticity mechanisms. Remarkably, this novel role of WOX11 in plant cell size control is independent of WOX11-adventitious rooting underlying disease tolerance.
synapse: interactive support on photoemission spectroscopy measurement and analysis for non-expert users
Authors: Masuda Takuma , Kobayashi Masaki , Yatani Koji
Published: October 2023

Photoemission spectroscopy, an experimental method based on the photoelectric effect, is now an indispensable technique used in various fields such as materials science, life science, medicine and nanotechnology. However, part of the experimental process of photoemission spectroscopy relies on experience and intuition, which is obviously a problem for novice users. In particular, photoemission spectroscopy experiments using high-brilliance synchrotron radiation as a light source are not easy for novice users because measurements must be performed quickly and accurately as scheduled within a limited experimental period. In addition, research on the application of information science methods to quantum data measurement, such as photoemission spectroscopy, is mainly aimed at the development of analysis methods, and few attempts have been made to clarify the problems faced by users who lack experience. In this study, the problems faced by novice users of photoemission spectroscopy are identified, and a native application named synapse with functions to solve these problems is implemented and evaluated qualitatively and quantitatively. This paper describes the contents of an interview survey, the functional design and the implementation of the application synapse based on the interview survey, and results and discussion of the evaluation experiment.
Sustainable building materials utilization in the construction sector and the implications on labour productivity
Authors: Adebowale Oluseyi Julius , Agumba Justus Ngala
Published: October 2023

Purpose

The United Nations has demonstrated a commitment to preserving the ecosystem through its 2030 sustainable development goals agenda. One crucial objective of these goals is to promote a healthy ecosystem and discourage practices that harm it. Building materials production significantly contributes to the emissions of greenhouse gases. This poses a threat to the ecosystem and prompts a growing demand for sustainable building materials (SBMs). The purpose of this study is to investigate SBMs to determine their utilization in construction operations and the potential impact their application could have on construction productivity.

Design/methodology/approach

A systematic review of the existing literature in the field of SBMs was conducted for the study. The search strings used were “sustainable” AND (“building” OR “construction”) AND “materials” AND “productivity”. A total of 146 articles were obtained from the Scopus database and reviewed.

Findings

Bio-based, cementitious and phase change materials were the main categories of SBMs. Materials in these categories have the potential to substantially contribute to sustainability in the construction sector. However, challenges such as availability, cost, expertise, awareness, social acceptance and resistance to innovation must be addressed to promote the increased utilization of SBMs and enhance construction productivity.

Originality/value

Many studies have explored SBMs, but there is a dearth of studies that address productivity in the context of SBMs, which leaves a gap in understanding. This study addresses this gap by drawing on existing studies to determine the potential implications that using SBMs could have on construction productivity.
Spectrophotometry and chromatography analyses combined with chemometrics tools to differentiate green coffee beans into special or traditional
Authors: Claro Gomes Winston Pinheiro , Gonçalves Bortoleto Gisele , Melchert Wanessa R.
Published: October 2023

Green coffee is the hulled coffee bean, rich in chemical compounds indicative of quality before roasting, making the classification special or traditional. This work aimed to determine compounds in green coffee beans and find the differentiation of green coffee beans into special or traditional ones through chemometrics. For that, the levels of phenolic compounds, reducing, nonreducing, and total sugars were quantified by spectrophotometry: caffeine, trigonelline, 5‐hydroxymethylfurfural (5‐HMF), 3‐hydroxybenzoic, 4‐hydroxybenzoic, chlorogenic, caffeic, and nicotinic acids (NAs) by high‐performance liquid chromatography–UV–Vis; acetaldehyde, acetone, methanol, ethanol, and isoamyl by HS‐GC‐FID. Principal component analysis (PCA) was used to differentiate green coffee beans through the levels obtained in spectrophotometric and chromatographic analyses. Statistically, the contents of total phenolic compounds, caffeine, nonreducing sugars, total sugars, NA, 5‐HMF, acetaldehyde, ethanol, and ethanol/methanol showed significant differences. The PCA made it possible to classify green coffee beans into special and traditional, in addition to understanding the attributes that influenced the differentiation between coffees. In addition, it was possible to classify green coffee beans into special and traditional, either using all parameters evaluated or only using spectrophotometric analyses. In this way, some advantages allow classification without using a trained and experienced evaluator as their previous experience can influence the results due to their expertise in a certain type of coffee, in addition to being faster and cheaper, especially regarding spectrophotometric analyses.
Anti‐osteoporosis effects of mammalian lignans and their precursors from flaxseed and safflower seed using zebrafish model
Authors: Yang Xin‐Yue , Wu Dan‐Dan , Zhuang Cong‐Cong , Ma Chao‐Mei
Published: October 2023

Secoisolariciresinol diglucoside (SDG) and tracheloside (TCL) are the main lignan components of flaxseed cake and safflower seed cake, which are by‐products of oil extraction. Both SDG and TCL are metabolized into mammalian lignan enterolactone (EL) with the involvement of intestinal bacteria. In this research, we evaluated the anti‐osteoporosis effects of SDG and the in vivo metabolites EL and enterodiol (ED) prepared in our previous work, as well as the newly isolated chemical constituents from safflower seed, including TCL, the lactone ring opening product of TCL (OTCL) and two alkaloids on the alloxan‐induced zebrafish model. All the compounds showed significant anti‐osteoporosis effects at 80 µM, with p < 0.05 for EL and p < 0.001 for other compounds compared with the model. SDG and TCL showed the most significant and concentration‐dependent effects, with p < 0.001 compared with model at 20 µM. The alkaloids, N‐coumaroylserotonin glucoside and N‐feruloylserotonin glucoside, also showed anti‐osteoporosis at 20 µM with p < 0.01, whereas EL, ED, and OTCL showed no significant effects. Quantitative real‐time polymerase chain reaction revealed that SDG and TCL upregulated the expression of osteogenic genes Runx2, SP7, OPG, Col1a1a, Alp, ON, OPN, and OCN in alloxan‐treated zebrafish. The in vivo metabolite of lignans, EL, showed significant anti‐inflammatory effect (p < 0.01) at 20 µM, which might also help to combat osteoporosis and other complications caused by excessive immune response in the body. The results provided scientific data for using the oil extraction by‐products as sources of anti‐osteoporosis compounds.

Practical Application

This study found that lignans in flaxseed cake and safflower seed cake exhibited anti‐osteoporosis effects by upregulating the expression of osteogenic genes, making the oil extraction by‐products sources of anti‐osteoporosis compounds.
Testicular function after non‐cytotoxic and immunotherapy drug treatment
Authors: Handelsman David J. , Idan Amanda , Sleiman Sue , Bacha Fey , Long Georgina V. , Menzies Alexander M. , Vaishnav Tejnei , Litkouhi Noosha , Volckmar Xanthie , Ledger William , Anazodo Antoinette
Published: October 2023

Background

The effects of novel non‐cytotoxic and immunotherapy drugs for cancer treatment on human testicular function have not been studied systematically.

Objectives

The present study aimed to characterize effects of non‐cytotoxic and immunotherapy drugs in patients with cancers who had not been previously treated with gonadotoxic chemo‐ or radiotherapy.

Materials and methods

This study involved 34 men, not previously treated with gonadotoxic regimens, in a mixed longitudinal (Cohort 1: 19 men about to start and approximately 1 year on non‐cytotoxic and immunotherapy treatment) and cross‐sectional (Cohort 2: 15 men already on non‐cytotoxic and immunotherapy treatment) study using data modeling to estimate within‐person time‐course changes in testicular exocrine and endocrine functions. Cohort 1 provided 45 paired semen and blood samples (34 prior to and nine during treatment) and Cohort 2 provided 45 sets of samples (15 pre‐treatment, 30 on treatment), including six men in Cohort 2 who had pre‐treatment spermatozoa cryostorage prior to the study. Men on non‐cytotoxic and immunotherapy treatment had undergone a median of 33.5 months long‐term treatment.

Results

Spermatozoa output and concentration were reduced by about 50%, with corresponding increases in serum follicle‐stimulating hormone and decreases in serum inhibin B. Serum testosterone, luteinizing hormone, and sex hormone‐binding globulin were unaffected by non‐cytotoxic and immunotherapy treatment.

Conclusion

Within limits of the present study of sample size and duration of on‐non‐cytotoxic and immunotherapy treatment, non‐cytotoxic and immunotherapy drugs have a modest effects on testicular exocrine function (sperm production) or its hormonal correlates (follicle‐stimulating hormone, inhibin B), with minimal impact on testicular endocrine (testosterone, luteinizing hormone) function.
Letter: A step forward towards a standard FMT protocol for IBS
Authors: El‐Salhy Magdy , Gilja Odd Helge , Hatlebakk Jan Gunnar
Published: October 2023

LINKED CONTENT

This article is linked to Yau et al paper. To view this article, visit https://doi.org/10.1111/apt.17703
Use of the anterior prostatic urethral mucosa preservation technique during holmium laser enucleation of the prostate can reduce postoperative stress urinary incontinence
Authors: Fujisaki Yukiya , Otsuka Isamu , Kobayashi Takahiko , Miyake Nao , Ito Kaoru , Terada Naoki , Kamoto Toshiyuki , Iwamoto Hideyasu
Published: October 2023

Introduction

Holmium laser enucleation of the prostate (HoLEP) is an effective and safe surgery for patients with benign prostatic hyperplasia. However, some patients exhibit postoperative urinary incontinence. Here, we compared surgical outcomes and incidence of stress urinary incontinence between HoLEP with and without anterior prostatic urethral mucosa preservation (APUMP).

Methods

All patients in this study underwent HoLEP with APUMP technique (APUMP group) and without APUMP technique (no‐APUMP group). Enucleation weight, enucleation time, max flow rate increase at 3 months, and urinary incontinence rates immediately after catheter removal and at 1 month after surgery were compared between the groups.

Results

In the APUMP (n = 340) and no‐APUMP (n = 75) groups, the median enucleation weights were 34.5 and 35.0 g, respectively (p = .982). The corresponding median enucleation times were 33.0 and 46.5 min (p < .01), and median max flow rate increases at 1 month were 10.5 and 9.9 mL/s (p = .89). The urinary incontinence rates immediately after catheter removal were 4.1% and 14.7% (p < .01), and were 3.8% and 12.0% (p < .01) at 1 month after surgery.

Conclusion

HoLEP using the APUMP technique could be performed with a shorter operative time while maintaining efficacy. The incidence of postoperative urinary incontinence could be decreased by APUMP, indicating that such preservation facilitates the maintenance of urinary continence after surgery.
Sleep spindles as neurophysiological biomarkers of schizophrenia
Authors: Ferrarelli Fabio
Published: October 2023

Schizophrenia (SCZ) is a complex psychiatric disorder characterized by a wide range of clinical symptoms, including disrupted sleep. In recent years, there has been growing interest in assessing alterations in sleep parameters in patients with SCZ. Sleep spindles are brief (0.5–2 s) bursts of 12‐ to 16‐Hz rhythmic electroencephalogram (EEG) oscillatory activity occurring during non‐rapid eye movement (NREM) sleep. Spindles have been implicated in several critical brain functions, including learning, memory and plasticity, and are thought to reflect the integrity of underlying thalamocortical circuits. This review aims to provide an overview of the current research investigating sleep spindles in SCZ. After briefly describing the neurophysiological features of sleep spindles, I will discuss alterations in spindle characteristics observed in SCZ, their associations with the clinical symptomatology of these patients and their putative underlying neuronal and molecular mechanisms. I will then discuss the utility of sleep spindle measures as predictors of treatment response and disease progression. Finally, I will highlight future directions for research in this emerging field, including the prospect of utilizing sleep spindles as neurophysiological biomarkers of SCZ.
Prevalence of pre‐eclampsia in 265 patients with an intracranial aneurysm, 393 female relatives versus a control cohort: A case–control study
Authors: Kotikoski Satu , Paavola Juho , Nurmonen Heidi J. , Kärkkäinen Virve , Huuskonen Terhi J. , Huttunen Jukka , Koivisto Timo , von und zu Fraunberg Mikael , Jääskeläinen Juha E. , Lindgren Antti E.
Published: October 2023

Background and objectives

There is emerging evidence on the connection between pre‐eclampsia and saccular intracranial aneurysms (sIAs). Our aim was to study the prevalence of pre‐eclampsia in sIA patients, their female relatives, and matched controls, and to examine familial sIA disease and familial pre‐eclampsia in sIA patients' families.

Methods

We included all female sIA patients in the Kuopio Intracranial Aneurysm Patient and Family Database from 1995 to 2018. First, we identified the sIA patients, their female relatives, and matched population controls with the first birth in 1987 or later and studied the prevalence of pre‐eclampsia. Second, all female sIA patients and all female relatives were analyzed for familial sIA disease and familial pre‐eclampsia. Using the Finnish nationwide health registries, we obtained data on drug purchases, hospital diagnoses, and causes of death.

Results

In total, 265 sIA patients, 57 daughters, 167 sisters, 169 nieces, and 546 matched controls had the first birth in 1987 or later. Among them, 29 (11%) sIA patients, 5 (9%) daughters, 10 (6%) sisters, 10 (6%) nieces, and 32 (6%) controls had pre‐eclampsia. Of all the 1895 female sIA patients and 12,141 female relatives, 68 sIA patients and 375 relatives had pre‐eclampsia, including 32 families with familial pre‐eclampsia.

Conclusions

Pre‐eclampsia was significantly more common in the sIA patients than in their matched controls. Familial sIA disease and familial pre‐eclampsia co‐occurred in seven families. Further studies of the mechanisms by which pre‐eclampsia could affect the walls of brain arteries and increase the rupture risk in sIA disease are indicated.
Assessing climatic and spatial variables influencing zooplankton richness for space‐for‐time predictions
Authors: Heuschele Jan , Andersen Tom , Walseng Bjørn , Hessen Dag O.
Published: October 2023

The macroecological drivers of freshwater diversity are accredited geographical, spatial and climatic variables, but also to productivity, ecosystem age and landscape history. Locally diversity is also influenced by the dispersal ability of species. Here we evaluated how spatial and climatic variables influence species richness and macroecological patterns in Cladocera and Copepoda. We also discuss whether a space‐for‐time approach is suitable to predict the community's response to the current rapid warming of lakes.

We use the presence‐absence of pelagic and littoral microcrustaceans in 1465 Norwegian lakes with a wide range of latitudinal, longitudinal, and altitudinal gradients, as well as a wide span in lake areas, to evaluate how spatial and climatic factors influence zooplankton diversity in two major groups: Cladocera and Copepoda.

Longitude and latitude per se were poor predictors of zooplankton richness, but a combination of spatial and ecological predictors gave a good spatial prediction of cladoceran and copepod richness. These two groups did, however, not differ in their spatial distribution, with a strikingly fixed proportion of copepods close to 0.3, suggesting no obvious Allee‐ effects regarding the mode of reproduction (asexual vs sexual).

Since temperature alone was a poor predictor of species richness for both groups and dispersal constraints can make it very difficult to estimate a new richness equilibrium under a future climate, space‐for‐time predictions may have limited value for assessing future patterns of microcrustacean diversity.

Based on a quite unique dataset in terms of the sheer number of sites, spatial gradients, and inclusion of littoral species, our study demonstrates that assessments on how changing climate will shape and modulate zooplankton communities in the future are problematic.
Farmers' adaptation and mitigation practices in the Upper Rhine Valley: Drivers, synergies and trade‐offs
Authors: Bohnert Gaël , Martin Brice
Published: October 2023

Through semi‐structured interviews, this work analyses the motives and drivers leading wine growers and crop farmers in the Upper Rhine Valley (France, Germany, Switzerland) to adopt climate change adaptation and mitigation practices. We show that the main motive is to adapt, seen from an individual and reactive point of view. However, these practices sometimes also bring negative side effects in the long term or on other actors, and considering other problematics. On the contrary, other farmers’ thinking is more anticipatory and they pay more attention to the common good. Nevertheless, they are not necessarily the most successful in adaptation in the short term as they often are more affected. This shows the limits of the concept of adaptation, as centred on individuals and eluding issues that are not related to climate change. That is why we prefer considering system transitions, taking into account the interactions between the diverse problematics and actors.
Sense of psychological ownership in co‐design processes: A case study
Authors: Juel Anette , Berring Lene L. , Erlangsen Annette , Larsen Erik R. , Buus Niels
Published: October 2023

Introduction

Service users are increasingly participating in health research. Although collaborative research is assumed to give users a sense of psychological ownership, little is known about the specific psychosocial processes through which ownership develops and is displayed. The present study yields insight into a process in which service users, researchers and a website designer collaborated to design a website.

Aim

The aim of this study was to explore how participants developed and displayed feelings of ownership during a collaborative process to design a website.

Methods

A case study design was adopted by which audio recordings were subjected to thematic analysis and interpreted by drawing on the concept of psychological ownership.

Findings

A sense of psychological ownership of the website design process emerged in two distinct and overlapping phases. In the first phase, ‘sense of ownership during the early design phase’, only researchers and the website designer displayed a sense of ownership, which was facilitated by the research context preceding the collaborative workshops. In the second phase, ‘sense of ownership during the collaborative design phase’, service users gradually started to develop parallel feelings of ownership that were facilitated by workshop design activities. These activities enabled service users to increasingly control the process, to invest themselves in the process and to gain intimate knowledge of the process and its outcome. Service users' sense of ownership was displayed in their statements about the website and its elements.

Conclusion

Participants engaged in codesign processes may develop a sense of psychological ownership at different speeds because of contextual factors. It is important to take this into account as it may complicate the formation of egalitarian work groups.

Patient and Public Contribution

Parents of children with suicidal behaviour and a counsellor participated as service users in a website design process.
Filtering low‐energy carriers to enhance thermoelectric performance of Cd‐doped SnSe via incorporation of MXene sheets
Authors: Qin Yi , Wang Mengxue , Li Xiaohan , Zhang Yajuan , Tang Shenglai , Zhu Jianfeng , Zhao Ting
Published: October 2023

SnSe‐based materials have attracted widespread attention in thermoelectrics due to their outstanding thermoelectric performance. However, the pristine and unmodified polycrystalline SnSe reveals poor electrical properties. Doping and constructing nanostructured composite architectures to produce energy filtering effect proved to be an effective method to strengthen thermoelectric performance. In this study, Ti3C2/Sn0.98Cd0.02Se composites are successfully fabricated by the solvothermal method combined with the electrostatic self‐assembly method and spark plasma sintering. The phase interface introduced by incorporating Ti3C2 into Sn0.98Cd0.02Se can effectively filter low‐energy carriers due to its generation of energy barriers, thereby the Seebeck coefficient of x wt% Ti3C2/Sn0.98Cd0.02Se x = (0.05, 0.5, 1) samples is better than that of the pristine Sn0.98Cd0.02Se over the whole temperature range. Meanwhile, high conductivity was also obtained in 1 wt% Ti3C2/Sn0.98Cd0.02Se sample so that the high power factor of 3.31 μWcm−1K−2 was acquired at 773 K. Ultimately, a peak ZT value of 0.41 was obtained at 773 K, compared with pristine Sn0.98Cd0.02Se, and the thermoelectric performance improved by 24%. This study offers an available approach to efficiently enhance the thermoelectric properties of polycrystalline SnSe‐based materials.
An elaborative discussion on the potentiality, functional characteristics, curative effects, antinutritional factors, processing, and industrial applications of faba beans (Vicia faba L.) as a versatile legume
Authors: Agrawal Swati , Panigrahi Chirasmita , Eri Rajaraman
Published: October 2023

Globally, 60% of protein consumption comes from plant‐based sources. By exploring the potential of plant‐based proteins and incorporating them into diverse food options, we can not only enhance the sustainability of our food systems but also contribute to a more balanced and environmentally conscious society. Due to the limited availability of conventional food proteins, there has been a persistent exploration for alternative legume sources for addressing the need for protein‐based foods. Faba bean is a type of pulse that stands out among other legumes due to its high protein content (26.1%) and dietary fibre (25.0%). Faba beans and their derivatives have been suggested as potentially beneficial foods for individuals with diabetes and hypertension. However, faba beans contain some antinutritional factors (ANFs). These antinutrients can have adverse effects on digestion and nutrient absorption. Various strategies like thermal and non‐thermal processing methods have been employed to reduce the ANF content and improve nutritional functionality in faba beans. The applications of faba beans and their potential as replacements for traditional ingredients in various food products are described. By utilising processed fava bean products, novel food formulations and applications can be created, catering to the growing demand for healthier and functional food options.
The prevalence of urinary incontinence and risk factors in menopausal women in Turkey: A systematic review and meta‐analysis
Authors: Karaçam Zekiye , Özsoy Sevgi , Özer Yurdal Nazlı Emel
Published: October 2023

This study was conducted to determine the prevalence and risk factors of urinary incontinence in menopausal women. This systematic review and meta‐analysis followed PRISMA and COSMOS‐E guidelines. The searches were conducted on 1–15 April, 2022 using PubMed, EBSCO, Embase, PsycINFO, DOAJ, Web of Science, DergiPark, Scopus, Turkish Medline, Turkish Citation Index, TR Index and National Thesis Center search engines. The keywords ‘menopause, climacteric, urinary incontinence, risk factors, prevalence’ were used in the searches. The risk of bias was assessed using the Critical Appraisal Checklist for cross‐sectional studies developed by the Joanna Briggs Institute. Data were synthesized by meta‐analysis, meta‐regression and narrative methods. Eleven studies published between 2012 and 2022 were included. The total sample size of the studies was 2531. In this meta‐analysis, the estimated rate of urinary incontinence in women aged 40–65 years was 46.9% (95% CI: 0.346–0.595), and this result was statistically significantly affected by the moderator variables risk of bias (Q = 8.76, p = 0.013) and urinary incontinence diagnostic tools (Q = 27.60, p < 0.001). The estimated stress urinary incontinence rate was 19.1% (95% CI: 0.130–0.271), urge urinary incontinence rate was 5.1% (95% CI: 0.020–0.124) and the mixed urinary incontinence rate was 13.4% (95% CI: 0.092–0.192). The risk factors affecting urinary incontinence were found to be advanced age, menopause, diabetes mellitus, constipation, obesity, history of urinary incontinence during pregnancy and the postpartum period, mode of delivery, four or more births, urinary tract infection, family history of urinary incontinence and genetic predisposition. This meta‐analysis revealed that urinary incontinence and its types are highly prevalent in women aged 40–65 years and that the prevalence is influenced by the quality of research and the type of diagnostic tool used in addition to many risk factors. Planning and offering appropriate health care services based on these results could contribute to the protection and improvement of women's health.
RETRACTED: Effects of application of the clinical nursing pathway on surgical site wound infection and postoperative complication rates in patients with total knee arthroplasty: A meta‐analysis
Authors: Han Jing , Liu Xin‐Ju
Published: October 2023

This study aimed to systematically evaluate the effects of clinical nursing on surgical site wound infections and postoperative complications in patients after undergoing total knee arthroplasty (TKA). Computerised searches of Embase, PubMed, Cochrane Library, China National Knowledge Infrastructure, VIP and Wanfang databases were conducted from inception to August 2023 to collect randomised controlled trials (RCTs) on patients with TKA who received clinical nursing pathway interventions. Literature screening, data extraction and quality assessment of the included studies were performed independently by two researchers. The meta‐analysis was performed using Stata 17.0. A total of 14 RCTs with 1174 patients were included, including 587 patients each in the intervention and control groups. The meta‐analysis results showed that the application of clinical nursing pathways to patients undergoing TKA significantly reduced surgical site wound infections (risk ratio [RR] = 0.28, 95% confidence interval [CI]: 0.15–0.54, p < 0.001) and postoperative complications (RR = 0.25, 95% CI: 0.17–0.37, p < 0.001). Therefore, clinical nursing pathway interventions in patients undergoing TKA should be promoted in clinical practice as they can effectively reduce the incidence of wound infection and postoperative complications.
Commonalities in the Reasons for Switching Advertising Agencies: Corroboratory Evidence from New Zealand
Authors: Durden G. , Orsman T. , Mitchell P.C.N.
Published: October 2023

Our replication study in New Zealand of failed advertising agency‐client relationships provides findings to support previous UK and US research that a common set of reasons appears to exist, both between countries and over time, to explain why breakups occur. Advertisers responsible for over half of advertising account switches in New Zealand between 1993 and 1994 gave identical rankings to their counterparts in the UK and USA on the general factors explaining breakups, and also similar ratings on the relative importance of the thirty‐five detailed variables associated with failure.