bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiotemporally programming cytokine immunotherapies through protein engineering
Authors: Santollani Luciano , Wittrup K. Dane
Published: July 2023

Cytokines have long been considered promising cancer immunotherapy agents due to their endogenous role in activating and proliferating lymphocytes. However, since the initial FDA approvals of Interleukin‐2 (IL‐2) and Interferon‐ɑ (IFNɑ) for oncology over 30 years ago, cytokines have achieved little success in the clinic due to narrow therapeutic windows and dose‐limiting toxicities. This is attributable to the discrepancy between the localized, regulated manner in which cytokines are deployed endogenously versus the systemic, untargeted administration used to date in most exogenous cytokine therapies. Furthermore, cytokines' ability to stimulate multiple cell types, often with paradoxical effects, may present significant challenges for their translation into effective therapies. Recently, protein engineering has emerged as a tool to address the shortcomings of first‐generation cytokine therapies. In this perspective, we contextualize cytokine engineering strategies such as partial agonism, conditional activation and intratumoral retention through the lens of spatiotemporal regulation. By controlling the time, place, specificity, and duration of cytokine signaling, protein engineering can allow exogenous cytokine therapies to more closely approach their endogenous exposure profile, ultimately moving us closer to unlocking their full therapeutic potential.
Classification and characterisation of extracellular vesicles‐related tuberculosis subgroups and immune cell profiles
Authors: Zhou Peipei , Shen Jie , Ge Xiao , Ding Fang , Zhang Hong , Huang Xinlin , Zhao Chao , Li Meng , Li Zhenpeng
Published: July 2023

Around the world, tuberculosis (TB) remains one of the most common causes of morbidity and mortality. The molecular mechanism ofMycobacterium tuberculosis(Mtb) infection is still unclear. Extracellular vesicles (EVs) play a key role in the onset and progression of many disease states and can serve as effective biomarkers or therapeutic targets for the identification and treatment of TB patients. We analysed the expression profile to better clarify the EVs characteristics of TB and explored potential diagnostic markers to distinguish TB from healthy control (HC). Twenty EVs‐related differentially expressed genes (DEGs) were identified, and 17 EVs‐related DEGs were up‐regulated and three DEGs were down‐regulated in TB samples, which were related to immune cells. Using machine learning, a nine EVs‐related gene signature was identified and two EVs‐related subclusters were defined. The single‐cell RNA sequence (scRNA‐seq) analysis further confirmed that these hub genes might play important roles in TB pathogenesis. The nine EVs‐related hub genes had excellent diagnostic values and accurately estimated TB progression. TB's high‐risk group had significantly enriched immune‐related pathways, and there were substantial variations in immunity across different groups. Furthermore, five potential drugs were predicted for TB using CMap database. Based on the EVs‐related gene signature, the TB risk model was established through a comprehensive analysis of different EV patterns, which can accurately predict TB. These genes could be used as novel biomarkers to distinguish TB from HC. These findings lay the foundation for further research and design of new therapeutic interventions aimed at treating this deadly infectious disease.
Environmental oestrogens disrupt testicular descent and damage male reproductive health: Mechanistic insight
Authors: Li Danli , Ping Hongyan , Li Ke , Lin Junjie , Jiang Xuewu , Zhang Xuan
Published: July 2023

Environmental oestrogens (EEs) as environmental pollutants have been paid much attention due to their impact on congenital malformation of male genitourinary system. Exposure to EEs for prolonged time could hinder testicular descent and cause testicular dysgenesis syndrome. Therefore, it is urgent to understand the mechanisms by which EEs exposure disrupt testicular descent. In this review, we summarize recent advances in our understanding of the process of testicular descent, which is regulated by intricate cellular and molecular networks. Increasing numbers of the components of these networks such as CSL and INSL3 are being identified, highlighting that testicular descent is a highly orchestrated process that is essential to human reproduction and survival. The exposure to EEs would lead to the imbalanced regulation of the networks and cause testicular dysgenesis syndrome such as cryptorchidism, hypospadias, hypogonadism, poor semen quality and testicular cancer. Fortunately, the identification of the components of these networks provides us the opportunity to prevent and treat EEs induced male reproductive dysfunction. The pathways that play an important role in the regulation of testicular descent are promising targets for the treatment of testicular dysgenesis syndrome.
Endoplasmic reticulum homeostasis—From molecules to organisms: Report on the 14th International Calreticulin Workshop, Saint Malo, France
Authors: Bakambamba Ketsia , Di Modugno Federico , Guilbard Marianne , Le Goupil Simon , Lhomond Stephanie , Pelizzari‐Raymundo Diana , Avril Tony , Chevet Eric , Delom Frédéric , Lafont Elodie
Published: July 2023

The Calreticulin Workshop, initiated in 1994 by Marek Michalak in Banff (Alberta, Canada), was first organized to be an informal scientific meeting attended by researchers working on diverse biological questions related to functions associated with the endoplasmic reticulum (ER)‐resident lectin‐like chaperone and applied to a wide range of biological systems and models. Since then, this workshop has broadened the range of topics to cover all ER‐related functions, has become international and has been held in Canada, Chile, Denmark, Italy, Switzerland, UK, USA, Greece and this year in France. Each conference, which is organized every other year (pending world‐wide pandemic), generally attracts between 50 and 100 participants, including both early career researchers and international scientific leaders to favour discussions and exchanges. Over the years, the International Calreticulin Workshop has become an important gathering of the calreticulin and ER communities as a whole. The 14th International Calreticulin Workshop occurred from May 9–12 in St‐Malo, Brittany, France, and has been highlighted by its rich scientific content and open‐minded discussions held in a benevolent atmosphere. The 15th International Calreticulin Workshop will be organized in 2025 in Brussels, Belgium.
Association between birth‐related factors and periodontitis in women: Korea National Health and Nutrition Examination Survey 2013–2018
Authors: Kim Na‐Yeong , Kim Ji‐Eun , Choi Choong‐Ho , Chung Ki‐Ho
Published: July 2023

Aim

Adult women experience several changes in physiological status, such as pregnancy and childbirth, during their life cycle. This study analyses the association between birth‐related factors (the number of childbirths, abortions and miscarriages) and periodontitis using data from the Korea National Health and Nutrition Examination Survey, which represents Korean adults.

Materials and Methods

The study used data from Korea National Health and Nutrition Examination Survey VI and VII (2013–2018) and included 10,072 women 19 years or older, with no missing data on the variables assessed. Periodontitis was defined according to the Community Periodontal Index (CPI) criteria. Multiple logistic regression analysis, adjusting for age, household income, education, alcohol consumption, smoking, stress, body mass index, waist circumference, hypertension, diabetes mellitus, an oral examination within 1 year, daily tooth brushing frequency, hygiene products and self‐perceived oral health as identified via logistic regression analyses, was performed to determine the association between birth‐related variables and periodontitis.

Results

In the crude model, the odds ratio (OR) showed a significantly increased risk of periodontitis (CPI ≥ 3) and severe periodontitis (CPI = 4) based on the number of childbirths, abortions and miscarriages (p < .05). After covariate adjustment, periodontitis (CPI ≥ 3) was associated with the number of childbirths (1: OR = 1.92; 95% confidence interval [CI]: 1.47–2.50; 2: OR = 2.03; 95% CI: 1.57–2.61; ≥3: OR = 2.11; 95% CI: 1.60–2.78). Furthermore, severe periodontitis (CPI = 4) was also associated with the number of childbirths (1: OR = 2.33; 95% CI: 1.24–4.38; 2: OR = 2.99; 95% CI: 1.62–5.52; ≥3: OR = 3.34; 95% CI: 1.79–6.21).

Conclusions

The findings of this large‐scale, nationally representative study suggest that the number of childbirths is associated with the severity of periodontitis. However, the relationship between the number of abortions and miscarriages and periodontitis (CPI ≥ 3) or severe periodontitis (CPI = 4) is not significant.
Rapid screening for resistance of maize inbred and hybrid lines against southern corn leaf blight
Authors: Shukuru Bitaisha Nakishuka , Archana T. S. , Kangela Alain Matazi
Published: July 2023

Bipolaris is one of the most important phytopathogenic fungal genera to cause disease in cereal crops. Southern corn leaf blight (SCLB) is a pandemic and widespread disease; it's found everywhere corn is grown, causing a noticeable reduction in crop yield. Most cultivated varieties of maize do not resist SCLB disease where it is reported. Nevertheless, previous researchers have reported some resistant varieties of maize. In this study, we tested inbred and hybrid lines collected from ICAR‐IIMR based in Ludhiana against the disease. The field experiment was setup using a Randomized Block Design with three replications in natural conditions. Here we evaluated lines by quantifying disease pressure, yield, and their attributes. Moreover, model‐based clustering allowed the identification of five groups. For the SCLB disease confirmation, infected maize leaves were collected and used for pathogen isolation, and a pure culture was maintained. Both disease assessment and data analysis focused more specifically on characters that showed significant differences between means, especially leaf area, percentage of leaf infection, disease incidence, disease severity, disease index by plot basis, number of grain rows formed per ear, weight of maize kernels per ear, each corn ear weight, shelling percentage, and grain yield. The two best clusters identified, namely Group 1 and Group 2, together comprise 11002, 11009, 11026, 11030, 11069, 11149, 11153, 11185, 11328, 11333, 11337, 11347, 11370, 11385, 11074, 11351, 11356, 11357, 11608, and Karav‐8523 lines. As per disease reaction, CM‐500 is individually one of the best lines in terms of SCLB resistance. Specific symptoms were clearly found on leaves, and pseudo‐septate conidia were observed under the microscope. Thus, several lines exhibited highly resistant reactions against SCLB, especially 11002, 11009, 11026, 11069, 11074, 11337, 11347, 11385, and CM‐500, and can still be recommended for farmers and in breeding programmes, for future usefulness as industries are complaining of maize shortages, and they present a great commercial potential.
Improving sleep after stroke: A randomised controlled trial of digital cognitive behavioural therapy for insomnia
Authors: Fleming Melanie K. , Smejka Tom , Macey Ellie , Luengo‐Fernandez Ramon , Henry Alasdair L. , Robinson Barbara , Kyle Simon D. , Espie Colin A. , Johansen‐Berg Heidi
Published: July 2023

Stroke is frequently accompanied by long‐term sleep disruption. We therefore aimed to assess the efficacy of digital cognitive behavioural therapy for insomnia to improve sleep after stroke. A parallel group randomised controlled trial was conducted remotely in participant's homes/online. Randomisation was online with minimisation of between‐group differences in age and baseline Sleep Condition Indicator‐8 score. In total, 86 community‐dwelling stroke survivors consented, of whom 84 completed baseline assessments (39 female, mean 5.5 years post‐stroke, mean 59 years old), and were randomised to digital cognitive behavioural therapy or control (sleep hygiene information). Follow‐up was at post‐intervention (mean 75 days after baseline) and 8 weeks later. The primary outcome was self‐reported insomnia symptoms, as per the Sleep Condition Indicator‐8 (range 0–32, lower numbers indicate more severe insomnia, reliable change 7 points) at post‐intervention. There were significant improvements in Sleep Condition Indicator‐8 for digital cognitive behavioural therapy compared with control (intention‐to‐treat, digital cognitive behavioural therapy n = 48, control n = 36, 5 imputed datasets, effect of group p ≤ 0.02,  = 0.07–0.12 [medium size effect], pooled mean difference = −3.35). Additionally, secondary outcomes showed shorter self‐reported sleep‐onset latencies and better mood for the digital cognitive behavioural therapy group, but no significant differences for self‐efficacy, quality of life or actigraphy‐derived sleep parameters. Cost‐effectiveness analysis found that digital cognitive behavioural therapy dominates over control (non‐significant cost savings and higher quality‐adjusted life years). No related serious adverse events were reported to the researchers. Overall, digital cognitive behavioural therapy for insomnia effectively improves sleep after stroke. Future research is needed to assess earlier stages post‐stroke, with a longer follow‐up period to determine whether it should be included as part of routine post‐stroke care. Clinicaltrials.gov NCT04272892.
Entrepreneurial identity and entrepreneurial action: A within‐person field study
Authors: Stevenson Regan , Guarana Cristiano L. , Lee Jaewook , Conder Savannah L. , Arvate Paulo , Bonani Charles
Published: July 2023

Entrepreneurial action theory establishes that effective entrepreneurship requires daily action. Yet, empirical research on the daily antecedents of entrepreneurial action is relatively absent from the literature. We develop an entrepreneurial identity intervention and a theoretical model which integrates entrepreneurial identity theory with integrative self‐control theory (ISCT). We theorize that an entrepreneurial identity intervention administered in the morning will increase entrepreneurial action throughout the day. Further, we develop and test hypotheses regarding two mediating pathways, a motivation‐based pathway that relies on the felt passion of the entrepreneur and a control capacity‐based pathway that is connected to the entrepreneur's cognitive flexibility. We conducted two studies to validate the effectiveness of our intervention (Studies 1a and 1b) and four studies to test the validity and effectiveness of our experimental materials and measures (Studies A1a, A1b, A1c, and 2a). Our main study investigates the daily antecedents and mechanisms of entrepreneurial action using a within‐individual field experiment with 201 entrepreneurs (1458 daily observations). Overall, we find more within‐person than between‐person variance in entrepreneurial identity, daily action, and hypothesized meditators. We discuss the theoretical and practical implications of our findings for the entrepreneurship and organizational behavior literatures.
Identification of the novel HLA‐DPB1*02:01:68 allele in a Greek individual
Authors: Kouniaki Diamanto , Tarassi Katerina , Kitsiou Vasiliki , Fotopoulos Konstantinos , Tsirogianni Alexandra
Published: July 2023

Characterization of the novel HLA‐DPB1*02:01:68 allele in a 27‐year‐old Greek hematopoietic stem cell transplant candidate.
Scleral fixation of a novel modified, injected canine intraocular lens by haptic capture, in 17 dogs
Authors: Lewin Gary A. , Dixon Christopher J.
Published: July 2023

Introduction

The aims of lens removal surgery are to re‐establish or preserve both a clear visual axis and emmetropic vision. Trans‐scleral intraocular lens (IOL) fixation has been described in cases where lens capsule instability precludes the insertion of a prosthetic intraocular lens into the lens capsule. Previous techniques have necessitated enlargement of the corneal incision to accommodate either a rigid polymethylmethacrylate IOL or an acrylic foldable IOL inserted using forceps. This paper reports the modification of an endocapsular IOL to be used as an injectable suture‐fixated IOL introduced through a 2.8 mm corneal incision.

Materials and Methods

All cases underwent lens extraction by phacoemulsification followed by removal of the unstable lens capsule. A PFI X4 IOL (Medicontur) was modified to create four open‐loop haptics. The IOL was injected into the anterior chamber, each haptic was captured in a loop of suture introduced ab externo, and the lens was sutured with four‐point fixation.

Results

The results from 20 eyes in 17 dogs are reported. Over an average follow‐up time of 14.5 months, vision was retained in 16/20 eyes. Vision was lost in four eyes due to corneal ulceration and ocular hypertension (1/20), retinal detachment (2/20), and Progressive Retinal Atrophy (1/20).

Conclusions

The modified PFI X4 proved suitable for injection and scleral fixation through a 2.8 mm corneal incision, with a success rate comparable to previously published techniques.
Masking release at 4 and 32 kHz in harbor seals associated with sinusoidal amplitude-modulated masking noise
Authors: Kastelein Ronald A. , Helder-Hoek Lean , Defillet Linde N. , Terhune John M. , Beutelmann Rainer , Klump Georg M.
Published: July 2023

Masking can reduce the efficiency of communication and prey and predator detection. Most underwater sounds fluctuate in amplitude, which may influence the amount of masking experienced by marine mammals. The hearing thresholds of two harbor seals for tonal sweeps (centered at 4 and 32 kHz) masked by sinusoidal amplitude modulated (SAM) Gaussian one-third octave noise bands centered around the narrow-band test sweep frequencies, were studied with a psychoacoustic technique. Masking was assessed in relation to signal duration, (500, 1000, and 2000 ms) and masker level, at eight amplitude modulation rates (1–90 Hz). Masking release (MR) due to SAM compared thresholds in modulated and unmodulated maskers. Unmodulated maskers resulted in critical ratios of 21 dB at 4 kHz and 31 dB at 32 kHz. Masked thresholds were similarly affected by SAM rate with the lowest thresholds and the largest MR being observed for SAM rates of 1 and 2 Hz at higher masker levels. MR was higher for 32-kHz maskers than for 4-kHz maskers. Increasing signal duration from 500 ms to 2000 ms had minimal effect on MR. The results are discussed with respect to MR resulting from envelope variation and the impact of noise in the environment on target signal detection.
Direct interaction of small non-coding RNAs CjNC140 and CjNC110 optimizes expression of key pathogenic phenotypes of
Campylobacter jejuni
Authors: Ruddell Brandon , Hassall Alan , Moss Walter N. , Sahin Orhan , Plummer Paul J. , Zhang Qijing , Kreuder Amanda J.
Published: July 2023

Small non-coding RNAs (sRNAs) are important players in modulating gene expression in bacterial pathogens, but their functions are largely undetermined in
Campylobacter jejuni
, an important cause of foodborne gastroenteritis in humans. In this study, we elucidated the functions of sRNA CjNC140 and its interaction with CjNC110, a previously characterized sRNA involved in the regulation of several virulence phenotypes of
C. jejuni
. Inactivation of CjNC140 increased motility, autoagglutination, L-methionine concentration, autoinducer-2 production, hydrogen peroxide resistance, and early chicken colonization, indicating a primarily inhibitory role of CjNC140 for these phenotypes. Apart from motility, all these effects directly contrasted the previously demonstrated positive regulation by CjNC110, suggesting that CjNC110 and CjNC140 operate in an opposite manner to modulate physiologic processes in
C. jejuni
. RNAseq and northern blotting further demonstrated that expression of CjNC140 increased in the absence of CjNC110, while expression of CjNC110 decreased in the absence of CjNC140, suggesting a possibility of their direct interaction. Indeed, electrophoretic mobility shift assay demonstrated a direct binding between the two sRNAs via GA- (CjNC110) and CU- (CjNC140) rich stem-loops. Additionally, RNAseq and follow-up experiments identified that CjNC140 positively regulates
p19
, which encodes a key iron uptake transporter in
Campylobacter
. Furthermore, computational analysis revealed both CjNC140 and CjNC110 are highly conserved in
C. jejuni,
and the predicted secondary structures support CjNC140 as a functional homolog of the iron regulatory sRNA, RyhB. These findings establish CjNC140 and CjNC110 as a key checks-and- balances mechanism in maintaining homeostasis of gene expression and optimizing phenotypes critical for
C. jejuni
pathobiology.

IMPORTANCE

Gene regulation is critical to all aspects of pathogenesis of bacterial disease, and small non-coding RNAs (sRNAs) represent a new frontier in gene regulation of bacteria. In
Campylobacter jejuni
, the role of sRNAs remains largely unexplored. Here, we investigate the role of two highly conserved sRNAs, CjNC110 and CjNC140, and demonstrate that CjNC140 displays a primarily inhibitory role in contrast to a primarily activating role for CjNC110 for several key virulence-associated phenotypes. Our results also revealed that the sRNA regulatory pathway is intertwined with the iron uptake system, another virulence mechanism critical for
in vivo
colonization. These findings open a new direction for understanding
C. jejuni
pathobiology and identify potential targets for intervention for this major foodborne pathogen.
Development of monoclonal antibody-based blocking ELISA for detecting SARS-CoV-2 exposure in animals
Authors: Yuan Fangfeng , Chen Chi , Covaleda Lina M. , Martins Mathias , Reinhart Jennifer M. , Sullivan Drew R. , Diel Diego G. , Fang Ying
Published: July 2023

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant threat to public health. Besides humans, SARS-CoV-2 can infect several animal species. Highly sensitive and specific diagnostic reagents and assays are urgently needed for rapid detection and implementation of strategies for prevention and control of the infection in animals. In this study, we initially developed a panel of monoclonal antibodies (mAbs) against SARS-CoV-2 nucleocapsid protein. To detect SARS-CoV-2 antibodies in a broad spectrum of animal species, an mAb-based blocking enzyme-linked immunosorbent assay (bELISA) was developed. Test validation using a set of animal serum samples with known infection status obtained an optimal percentage of inhibition cut-off value of 17.6% with diagnostic sensitivity of 97.8% and diagnostic specificity of 98.9%. The assay demonstrates high repeatability as determined by a low coefficient of variation (7.23%, 4.89%, and 3.16%) between-runs, within-run, and within-plate, respectively. Testing of samples collected over time from experimentally infected cats showed that the bELISA was able to detect seroconversion as early as 7 days post-infection. Subsequently, the bELISA was applied for testing pet animals with coronavirus disease 2019 (COVID-19)-like symptoms and specific antibody responses were detected in two dogs. The panel of mAbs generated in this study provides a valuable tool for SARS-CoV-2 diagnostics and research. The mAb-based bELISA provides a serological test in aid of COVID-19 surveillance in animals.

IMPORTANCE

Antibody tests are commonly used as a diagnostic tool for detecting host immune response following infection. Serology (antibody) tests complement nucleic acid assays by providing a history of virus exposure, no matter symptoms developed from infection or the infection was asymptomatic. Serology tests for COVID-19 are in high demand, especially when the vaccines become available. They are important to determine the prevalence of the viral infection in a population and identify individuals who have been infected or vaccinated. ELISA is a simple and practically reliable serological test, which allows high-throughput implementation in surveillance studies. Several COVID-19 ELISA kits are available. However, they are mostly designed for human samples and species-specific secondary antibody is required for indirect ELISA format. This paper describes the development of an all species applicable monoclonal antibody (mAb)-based blocking ELISA to facilitate the detection and surveillance of COVID-19 in animals.
Identification of IMP Dehydrogenase as a Potential Target for Anti-Mpox Virus Agents
Authors: Hishiki Takayuki , Morita Takeshi , Akazawa Daisuke , Ohashi Hirofumi , Park Eun-Sil , Kataoka Michiyo , Mifune Junki , Shionoya Kaho , Tsuchimoto Kana , Ojima Shinjiro , Azam Aa Haeruman , Nakajima Shogo , Kawahara Madoka , Yoshikawa Tomoki , Shimojima Masayuki , Kiga Kotaro , Maeda Ken , Suzuki Tadaki , Ebihara Hideki , Takahashi Yoshimasa , Watashi Koichi
Published: July 2023

Mpox is a zoonotic disease caused by infection with the mpox virus, and a worldwide outbreak occurred in May 2022. The smallpox vaccine has recently been approved for clinical use against mpox in the United States.
Effect of Drinking Water Salt Content on the Interaction between Surfactants and Bacteria
Authors: Shteindel Nimrod , Silberbush Alon , Gerchman Yoram
Published: July 2023

Surface-adhering bacteria are a reoccurring problem in many settings, including households, municipal water systems, food production facilities, and hospitals. Surfactants, and specifically sodium dodecyl sulfate (also known as SDS/SLS), are commonly used to remove bacterial contamination, but data regarding the interaction of SDS with bacteria and especially the effects of water-dissolved salts on this interaction are lacking.
Intratumoral Microbiota Changes with Tumor Stage and Influences the Immune Signature of Oral Squamous Cell Carcinoma
Authors: Pratap Singh Raghwendra , Kumari Naina , Gupta Sameer , Jaiswal Riddhi , Mehrotra Divya , Singh Sudhir , Mukherjee Souvik , Kumar Rashmi
Published: July 2023

The gut microbiome has been explored extensively for its importance in the modulation of systemic inflammation and immune response; in contrast, the intratumoral microbiome is less studied for its influence on immunity in cancer. Given the established correlation between intratumoral lymphocyte infiltration and patient survival in cases of solid tumors, it was pertinent to explore the extrinsic factor influencing immune cell infiltration in the tumor.
Li isotope ratios of spring fluids as an effective tracer of slab-derived subducted sources across the Costa Rica forearc
Authors: Helper Jacob P. , Barnes Jaime D. , de Moor J. Maarten , Rodríguez Alejandro , Barry Peter H. , Ramos Evan J. , Lassiter John C.
Published: July 2023

Spring waters from across the Costa Rica margin were analyzed for their Li and He isotope compositions to determine the utility of Li isotopes as a tracer of volatile sources in subduction zones. Li isotope ratios systematically decrease with increasing depth to the subducting slab: averaging +15.0‰ ± 9.2‰ in the outer forearc (<40 km to the slab), +9.3‰ ± 4.3‰ in the forearc (40–80 km to the slab), and +5.8‰ ± 2.8‰ in the arc (>80 km to the slab). In contrast, air-corrected 3He/4He values (reported relative to the ratio in air, RA) range from 0.4 to 7.5 RA and increase from predominantly crustal values near the trench to mantle values in the arc. Together, these data support progressive devolatilization of the subducting plate with slab-derived Li components sourced from shallowly expelled pore fluids in the outer forearc, sedimentary and/or altered oceanic crust contributing to the forearc, and limited slab input beneath the arc.
Supplemental Material: Fluid-fluxed melting in the Himalayan orogenic belt: Implications for the initiation of E-W extension in southern Tibet
Authors: Gao Li-E , al. et
Published: July 2023

Supplemental Text S1: Analytical Methods. Figure S1: Cathodoluminescence (CL) showing the texture, spot, and respective age of zircon U-Pb dating for the leucogranites from the Cona and Everest regions along the Himalayan orogenic belt. Figure S2: U-Pb Concordia diagrams showing the crystallization ages of the representative leucogranites derived from fluid-absent melting (Group A) from the Cona and Everest regions along the Himalayan orogenic belt. Figure S3: Sr-Nd isotope systematics of the two types of leucogranites from the Malashan, Cona, and Everest regions along the Himalayan orogenic belt. Table S1: Summary of SHRIMP zircon U-Pb isotope data for the leucogranite in the Himalayan orogenic belt. Table S2: Summary of MC-ICP-MS zircon U-Pb isotope data for the leucogranite in the Himalayan orogenic belt. Table S3: Major and trace element compositions, as well as Sr-Nd isotope compositions of the leucogranite in the Himalayan orogenic belt.
Nutritional blindness from avoidant-restrictive food intake disorder – recommendations for the early diagnosis and multidisciplinary management of children at risk from restrictive eating
Authors: Schimansky Sarah , Jasim Haneen , Pope Lucy , Hinds Philippa , Fernandez Daphin , Choleva Paraskevi , Dev Borman Arundhati , Sharples Peta M , Smallbone Todd , Atan Denize
Published: July 2023

Avoidant-restrictive food intake disorder (ARFID) is an eating disorder characterised by limited consumption or the avoidance of certain foods, leading to the persistent failure to meet the individual’s nutritional and/or energy needs. The disordered eating is not explained by the lack of available food or cultural beliefs. ARFID is often associated with a heightened sensitivity to the sensory features of different types of food and may be more prevalent among children with autism spectrum disorder (ASD) for this reason. Sight loss from malnutrition is one of the most devastating and life-changing complications of ARFID, but difficult to diagnose in young children and those with ASD who have more difficulty with communicating their visual problems to carers and clinicians, leading to delayed treatment and greater probability of irreversible vision loss. In this article, we highlight the importance of diet and nutrition to vision and the diagnostic and therapeutic challenges that clinicians and families may face in looking after children with ARFID who are at risk of sight loss. We recommend a scaled multidisciplinary approach to the early identification, investigation, referral and management of children at risk of nutritional blindness from ARFID.
Navigation-guided transcaruncular orbital optic canal decompression in indirect traumatic optic neuropathy: long-term outcomes
Authors: Bhattacharjee Kasturi , Soni Deepak , Venkatraman Vatsalya , Grewal Aditi Mehta , Rehman Obaidur , Bhattacharjee Pragya , Bhattacharjee Harsha
Published: July 2023

Purpose

To determine the surgical outcomes using navigation-guided transcaruncular orbital optic canal decompression (NGTcOCD) and investigate the relationship between visual prognosis. visual evoked potential (VEP), association with DeLano type of optic canal and Onodi cells in patients with indirect traumatic optic neuropathy (TON).

Design

Prospective observational.

Methods

Fifty-two consecutive patients with indirect TON unresponsive to steroid therapy were divided into three groups where Group I comprised of cases with optic canal fracture who underwent NGTcOCD, Group II without optic canal fracture who underwent NGTcOCD and Group III, no-decompression group who chose not to undergo NGTcOCD. An improvement in visual acuity (VA) at 1 week, 3 months and 1 year and amplitude and latency of VEP at 1 year were considered as primary and secondary outcomes, respectively.

Results

The mean VA improved from 2.55±0.67 and 2.62±0.56 LogMAR at presentation to 2.03±0.96 and 2.33±0.72 LogMAR at final follow-up among Group I and Group II patients, respectively (p<0.001 and p=0.01). Statistically significant improvement observed among both the Groups in VEP amplitude (p=<0.01) and among Group II in VEP latency (p<0.01). Both Group I and Group II patients have better outcomes than patients in no-decompression group. VA at presentation and Type 1 DeLano optic canal were observed as significant prognostic factors.

Conclusions

NGTcOCD serves as a minimally invasive transcaruncular route to the optic canal which enables ophthalmologists to perform decompression from the anterior-most orbital end under direct visualisation. Patients with indirect TON with or without optic canal fracture and unresponsive to steroid therapy when managed with NGTcOCD have shown comparable and superior outcomes.
Did the Acute Frailty Network improve outcomes for older people living with frailty? A staggered difference-in-difference panel event study
Authors: Street Andrew , Maynou Laia , Conroy Simon
Published: July 2023

Objectives

To evaluate whether the Acute Frailty Network (AFN) was more effective than usual practice in supporting older people living with frailty to return home from hospital sooner and healthier.

Design

Staggered difference-in-difference panel event study allowing for differential effects across intervention cohorts.

Setting

All English National Health Service (NHS) acute hospital sites.

Participants

All 1 410 427 NHS patients aged 75+ with high frailty risk who had an emergency hospital admission to acute, general or geriatric medicine departments between 1 January 2012 and 31 March 2019.

Intervention

Membership of the AFN, a quality improvement collaborative designed to support acute hospitals in England deliver evidence-based care for older people with frailty. 66 hospital sites joined the AFN in six sequential cohorts, the first starting in January 2015, the sixth in May 2018. Usual care was delivered in the remaining 248 control sites.

Main outcome measures

Length of hospital stay, in-hospital mortality, institutionalisation, hospital readmission.

Results

No significant effects of AFN membership were found for any of the four outcomes nor were there significant effects for any individual cohort.

Conclusions

To realise its aims, the AFN might need to develop better resourced intervention and implementation strategies.
Regional variations in inpatient decompensated cirrhosis mortality may be associated with access to specialist care: results from a multicentre retrospective study
Authors:   The Trainee Collaborative for Research and Audit in Hepatology UK
Published: July 2023

Introduction

Specialist centres have been developed to deliver high-quality Hepatology care. However, there is geographical inequity in accessing these centres in the United Kingdom (UK). We aimed to assess the impact of these centres on decompensated cirrhosis patient outcomes and understand which patients transfer to specialist centres.

Methods

A UK multicentred retrospective observational study was performed including emergency admissions for patients with decompensated cirrhosis in November 2019. Admissions were grouped by specialist/non-specialist centre designation, National Health Service region and whether a transfer to a more specialist centre occurred or not. Univariable and multivariable comparisons were made.

Results

1224 admissions (1168 patients) from 104 acute hospitals were included in this analysis. Patients at specialist centres were more likely to be managed by a Consultant Gastroenterologist/Hepatologist on a Gastroenterology/Hepatology ward. Only 24 patients were transferred to a more specialist centre. These patients were more likely to be admitted for gastrointestinal bleeding and were not using alcohol. Specialist centres eliminated regional variations in mortality which were present at non-specialist centres. Low specialist Consultant staffing numbers impacted mortality at non-specialist centres (aOR 2.15 (95% CI 1.18 to 4.07)) but not at specialist centres. Hospitals within areas of high prevalence of deprivation were more likely to have lower specialist Consultant staffing numbers.

Conclusions

Specialist Hepatology centres improve patient care and standardise outcomes for patients with decompensated cirrhosis. There is a need to support service development and care delivery at non-specialist centres. Formal referral pathways are required to ensure all patients receive access to specialist interventions.
Treatment of adenoma recurrence after endoscopic mucosal resection
Authors: Tate David J , Desomer Lobke , Argenziano Maria Eva , Mahajan Neha , Sidhu Mayenaaz , Vosko Sergei , Shahidi Neal , Lee Eric , Williams Stephen J , Burgess Nicholas G , Bourke Michael J
Published: July 2023

Objective

Residual or recurrent adenoma (RRA) after endoscopic mucosal resection (EMR) of large non-pedunculated colorectal polyps (LNPCPs) of ≥20 mm is a major limitation. Data on outcomes of the endoscopic treatment of recurrence are scarce, and no evidence-based standard exists. We investigated the efficacy of endoscopic retreatment over time in a large prospective cohort.

Design

Over 139 months, detailed morphological and histological data on consecutive RRA detected after EMR for single LNPCPs at one tertiary endoscopy centre were prospectively recorded during structured surveillance colonoscopy. Endoscopic retreatment was performed on cases with evidence of RRA and was performed predominantly using hot snare resection, cold avulsion forceps with adjuvant snare tip soft coagulation or a combination of the two.

Results

213 (14.6%) patients had RRA (168 (78.9%) at first surveillance and 45 (21.1%) thereafter). RRA was commonly 2.5–5.0 mm (48.0%) and unifocal (78.7%). Of 202 (94.8%) cases which had macroscopic evidence of RRA, 194 (96.0%) underwent successful endoscopic therapy and 161 (83.4%) had a subsequent follow-up colonoscopy. Of the latter, endoscopic therapy of recurrence was successful in 149 (92.5%) of 161 in the per-protocol analysis, and 149 (73.8%) of 202 in the intention-to-treat analysis, with a mean of 1.15 (SD 0.36) retreatment sessions. No adverse events were directly attributable to endoscopic therapy. Further RRA after endoscopic therapy was endoscopically treatable in most cases. Overall, only 9 (4.2%, 95% CI 2.2% to 7.8%) of 213 patients with RRA required surgery.

Thus 159 (98.8%, 95% CI 95.1% to 99.8%) of 161 cases with initially successful endoscopic treatment of RRA and follow-up remained surgery-free for a median of 13 months (IQR 25.0) of follow-up.

Conclusions

RRA after EMR of LNPCPs can be effectively treated using simple endoscopic techniques with long-term adenoma remission of >90%; only 16% required retreatment. Therefore, more technically complex, morbid and resource-intensive endoscopic or surgical techniques are required only in selected cases.

Trial registration numbers

NCT01368289andNCT02000141
Low-intensity daily smoking and mortality risk among Mexican women
Authors: Gutiérrez-Torres Daniela Sarahí , Brochier Marion , Stern Dalia , Cortés-Valencia Adrian , Hernández-Ávila Juan Eugenio , Morales-Carmona Evangelina , Barrientos-Gutierrez Tonatiuh , Inoue-Choi Maki , Lajous Martin , Freedman Neal D
Published: July 2023

Objective

To examine the association between low-intensity smoking (10 or less cigarettes per day) and all-cause and cause-specific mortality risk among women who smoke and by age at cessation among women who previously smoked.

Methods

In this study, 104 717 female participants of the Mexican Teachers’ Cohort Study were categorised according to self-reported smoking status at baseline (2006/2008) and were followed for mortality through 2019. We estimated HRs and 95% CIs for all-cause and cause-specific mortality using multivariable Cox proportional hazards regression models with age as the underlying time metric.

Results

Smoking as few as one to two cigarettes per day was associated with higher mortality risk for all causes (HR: 1.36; 95% CI 1.10 to 1.67) and all cancers (HR: 1.46; 95% CI 1.05 to 2.02), compared with never smoking. Similarly, slightly higher HRs were observed among participants smoking ≥3 cigarettes per day (all causes HR: 1.43; 95% CI 1.19 to 1.70; all cancers HR: 1.48; 95% CI 1.10 to 1.97; cardiovascular disease HR: 1.58; 95% CI 1.09 to 2.28).

Conclusions

In this large study of Mexican women, low-intensity smoking was associated with higher mortality risk for all causes and all cancers. Interventions are needed to promote cessation among women who smoke at low-intensity in Mexico, regardless of how few cigarettes they smoke per day.
Shorebirds exhibit niche partitioning on multiple dimensions at a small staging site on the Northumberland Strait, New Brunswick, Canada
Authors: Bellefontaine Sara C. , Hamilton Diana J.
Published: July 2023

Animal populations take advantage of environmental heterogeneity to partition themselves into microhabitat niches. Such partitioning plays an important role in regulating interspecific competition and community structure by allowing multiple species to coexist. Atlantic Canada has many small coastal staging sites that host southbound migrant shorebirds. However, most shorebird studies in the region have been focused on larger sites in the Bay of Fundy, resulting in limited knowledge about staging ecology at these small sites, which often host more diverse shorebird assemblages. We examined niche partitioning by shorebirds on the Northumberland Strait, New Brunswick, Canada, to better understand how small coastal staging sites support diverse shorebird populations. We found evidence of partitioning on three niche dimensions: space, foraging behaviour, and diet. Most species specialized in at least one dimension, with foraging constraints based on bill morphology and habitat access based on species size likely driving segregation. Environmental heterogeneity at sites on the Northumberland Strait created multiple dimensions for segregation and fulfilled the niche requirements of diverse shorebird species during migratory staging. These findings broaden our understanding of staging ecology of multispecies flocks and suggest that conservation of small coastal sites is important for success of migratory shorebirds in Atlantic Canada.
A black hole toy model with non-local and boundary modes from non-trivial boundary conditions
Authors: Cheng Peng
Published: July 2023

We study gauge theories between two parallel boundaries with non-trivial boundary conditions, which serve as a toy model for black hole background with two boundaries near the horizon and infinite, aiming for a better understanding of the Bekenstein–Hawking entropy. The new set of boundary conditions allows boundary modes and non-local modes that interplay between the two boundaries. Those boundary modes and Wilson lines stretched between the two boundaries are carefully analyzed and are confirmed as physical variables in the phase space. Along with bulk fluctuation modes and topological modes, the partition function and entropy of all physical modes are evaluated via Euclidean path integral. It is shown that there are transitions between the dominance of different modes as we vary the temperature. The boundary fluctuation modes whose entropy is proportional to the volume dominate at high temperatures, and the boundary-area scaled boundary modes and Wilson lines are the more important at low temperatures. At super-low temperatures, when all the fluctuation modes die off, we see the topological modes whose entropy is the logarithm of the length scales of the system. The boundary modes and non-local modes should have their counterparts in a black hole system with similar boundary conditions, which might provide important hints for black hole physics.
Quasiperiodic oscillations around hairy black holes in Horndeski gravity
Authors: Rayimbaev Javlon , Dialektopoulos Konstantinos F. , Sarikulov Furkat , Abdujabbarov Ahmadjon
Published: July 2023

Testing gravity theories and their parameters using observations is an important issue in relativistic astrophysics. In this context, we investigate the motion of test particles and their harmonic oscillations in the spacetime of non-rotating hairy black holes (BHs) in Hordeski gravity, together with astrophysical applications of quasiperiodic oscillations (QPOs). We show possible values of upper and lower frequencies of twin-peak QPOs which may occur in the orbits from innermost stable circular orbits to infinity for various values of the Horndeski parameter q in relativistic precession, warped disk models, and three different sub-models of the epicyclic resonant model. We also study the behaviour of the QPO orbits and their position relative to innermost stable circular orbits (ISCOs) with respect to different values of the parameter q. It is obtained that at a critical value of the Horndeski parameter ISCO radius takes 6M which has been in the pure Schwarzschild case. Finally, we obtain mass constraints of the central BH of microquasars GRS 1915+105 and XTE 1550-564 at the GR limit and the possible value of the Horndeski parameter in the frame of the above-mentioned QPO models. The analysis of orbits of twin peak QPOs with the ratio of upper and lower frequencies 3:2, around the BHs in the frame of relativistic precession (RP) and epicyclic resonance (ER4) QPO models have shown that the orbits locate close to the ISCO. It is obtained that the distance between QPO orbits and ISCO is less than the error of the observations.
A spatially constrained QCD colour reconnection in $$\textrm{pp}$$, $$\textrm{p}A$$, and $$AA$$ collisions in the Pythia8/Angantyr model
Authors: Lönnblad Leif , Shah Harsh
Published: July 2023

We present an updated version of the QCD-based colour reconnection model in Pythia8, where we constrain the range in impact parameter for which reconnections are allowed. In this way, we can introduce more realistic colour reconnections in the Angantyr model for heavy ion collisions, where previously only reconnections within separate nucleon sub-collisions have been allowed. We investigate how the new impact parameter constraint influences final states in $$\textrm{pp}$$
pp
collisions, and retune parameters of the multi-parton interaction parameters in Pythia to compensate so that minimum bias data are reproduced. We also study multiplicity distributions in $$\textrm{p}A$$

p
A

collisions and find that, in order to counteract the loss in multiplicity due to the introduction of global colour reconnections, we need to modify some parameters in the Angantyr model while keeping the parameters tuned to $$\textrm{pp}$$
pp
fixed. With Angantyr we can then extrapolate to $$AA$$

AA

collisions without further parameter tuning and retaining a reasonable description of the basic multiplicity distributions.
You are What you Play: The Risks of Identity Fusion in Toxic Gamer Cultures
Authors: Kowert Rachel , Martel Alexi , Swann William B.
Published: July 2023

There has long been concern about the potential negative uses and effects of digital games. While these discussions have historically focused on the role of game content, it is the social environment of games that poses a more immediate concern. Specifically, the normalization of hateful behavior in gamer cultures. While “gamer cultures” originally developed as an identity to unite a group of so-called misfits who spent their time in shared physical, gaming spaces, today gamer cultures have come to be more associated with exclusion more than inclusion. In this piece we explore game cultures through the lens of identity fusion to explore the nature and influence of these identities.