bluuebunny/crossref_metadata_2025 huggingface dataset:
Significant histological disease of patients with chronic hepatitis B virus infection in the grey zone
Authors: Wang Jian , Yan Xiaomin , Zhu Li , Liu Jiacheng , Qiu Yuanwang , Li Yiguang , Liu Yilin , Xue Ruifei , Zhan Jie , Jiang Suling , Geng Yu , Wan Yawen , Li Ming , Mao Minxin , Gao Dongmei , Yin Shengxia , Tong Xin , Xia Juan , Ding Weimao , Chen Yuxin , Li Jie , Zhu Chuanwu , Huang Rui , Wu Chao
Published: November 2022

Background

Many patients with chronic hepatitis B (CHB) do not meet the definitions of the traditional natural phases and are classified as being in the grey zone (GZ).

Aims

To investigate liver histology, and to establish a management strategy for patients with CHB in the GZ.

Methods

This study included 1043 patients with CHB who underwent liver biopsy. Phases of natural history were determined according to the AASLD 2018 hepatitis B guidance. CHB patients in the GZ were divided into HBeAg‐positive, normal ALT and HBV DNA ≤106 IU/ml (GZ‐A); HBeAg‐positive, elevated ALT and HBV DNA ≤2 × 104 IU/ml (GZ‐B); HBeAg‐negative, normal ALT and HBV DNA ≥2 × 103 IU/ml (GZ‐C) and HBeAg‐negative, elevated ALT and HBV DNA ≤2 × 103 IU/ml (GZ‐D). Significant histological disease was defined as liver inflammation ≥G2 and/or liver fibrosis ≥S2.

Results

Two hundred and forty two (23.2%) patients were in the GZ. Approximately 72.7% had significant histological disease. HBeAg‐positive GZ CHB patients had a higher proportion of significant histological disease than HBeAg‐negative GZ patients (91.1% vs. 68.5%, p = 0.002). GZ‐D (42.6%) was the dominant category, followed by GZ‐C (38.8%), GZ‐A (10.3%) and GZ‐B (8.3%). The highest proportion of significant histological disease was observed patients in GZ‐B (100.0%), followed by GZ‐A (84.0%), GZ‐D (69.9%) and GZ‐C (67.0%). Prothrombin time (PT) was an independent risk factor of significant histological disease in the HBeAg‐negative GZ.

Conclusions

Over 70% of GZ CHB patients had significant histological disease. We recommend antiviral treatment for HBeAg‐positive and HBeAg‐negative GZ CHB patients with high PT.
Elucidating the cellular uptake mechanisms of heptamethine cyanine dye analogues for their use as an anticancer drug‐carrier molecule for the treatment of glioblastoma
Authors: Cooper Elizabeth , Choi Peter J. , Hwang Kihwan , Nam Kyung M. , Kim Chae‐Yong , Shaban Tina , Schweder Patrick , Mee Edward , Correia Jason , Turner Clinton , Faull Richard L. M. , Denny William A. , Noguchi Katsuya , Dragunow Mike , Jose Jiney , Park Thomas I.‐H.
Published: November 2022

The development of chemotherapies for glioblastoma is hindered by their limited bioavailability and toxicity on normal brain function. To overcome these limitations, we investigated the structure‐dependent activity of heptamethine cyanine dyes (HMCD), a group of tumour‐specific and BBB permeable near‐infrared fluorescent dyes, in both commercial (U87MG) and patient‐derived GBM cell lines. HMCD analogues with strongly ionisable sulphonic acid groups were not taken up by patient‐derived GBM cells, but were taken up by the U87MG cell line. HMCD uptake relies on a combination of transporter uptake through organic anion‐transporting polypeptides (OATPs) and endocytosis into GBM cells. The uptake of HMCDs was not affected by p‐glycoprotein efflux in GBM cells. Finally, we demonstrate structure‐dependent cytotoxic activity at high concentrations (EC50: 1–100 μM), likely due to mitochondrial damage‐induced apoptosis. An in vivo orthotopic glioblastoma model highlights tumour‐specific accumulation of our lead HMCD, MHI‐148, for up to 7 days following a single intraperitoneal injection. These studies suggest that strongly ionisable groups like sulphonic acids hamper the cellular uptake of HMCDs in patient‐derived GBM cell lines, highlighting cell line‐specific differences in HMCD uptake. We envisage these findings will help in the design and structural modifications of HMCDs for drug‐delivery applications for glioblastoma.
Fertility and pregnancy outcomes in women with nonclassic 21‐hydroxylase deficiency
Authors: Carrière Camille , Nguyen Lee S. , Courtillot Carine , Tejedor Isabelle , Chakhtoura Zeina , Bellanné‐Chantelot Christine , Tardy Véronique , Leban Monique , Touraine Philippe , Bachelot Anne
Published: November 2022

Introduction

Overall fertility and pregnancy outcomes in patients with nonclassic congenital adrenal hyperplasia (NCCAH) have been poorly studied. It has been suggested that hydrocortisone (HC) may decrease the time to conceive (TTC) and the rate of miscarriage in these patients.

Objectives

To describe fertility and pregnancy outcomes in a large cohort of NCCAH women. The secondary objective was to identify factors that could impact reproductive outcomes, with a particular focus on HC dose and genetic status.

Design

Retrospective study in a referral center for congenital adrenal hyperplasia.

Patients and Measurements

One hundred seventy‐three female patients with NCCAH confirmed by genetic testing, followed in our center between 2010 and 2019.

Results

Among the 173 patients, 95 women had a parental project, 86 of whom presented 176 pregnancies, 56% under glucocorticoid (GC) treatment and 44% without, and 76 women obtained 128 live births. Two‐thirds of the patients regularized their cycle under GC treatment, with significant decrease of androgens and progesterone levels. This treatment was associated with a shortening of TTC (coef β = −.196, information coefficient [IC] = [−10.7; −0.91], p = .021). Androgen levels and TTC were positively correlated to the rate of miscarriage (OR = 4.8, IC = [1.15; 20.34], p = .021 for testosterone, OR = 1.4, IC = [1.05; 1.81], p = .02 for androstenedione, and OR = 1.03, IC = [1.01; 1.06], p = .015 for TTC). There was no difference in terms of obstetric outcomes between patients with or without GC treatment. CYP21A2 genotype had no impact on pregnancy outcome or TTC.

Conclusions

Infertility is relative in patients with NCCAH. HC seems beneficial for fertility and pregnancy outcomes, especially for patients with menstrual disorders and high preconceptional androgen levels.
Ribavirin aerosol in hospitalized adults with respiratory distress and COVID‐19: An open‐label trial
Authors: Poulakou Garyfallia , Barakat Maxime , Israel Robert J. , Bacci Marcelo R. ,   Virazole Collaborator Group for COVID‐19 Respiratory Distress
Published: November 2022

There is an unmet medical need for effective treatments for hospitalized patients with coronavirus disease 2019 (COVID‐19). Ribavirin is a broad‐spectrum antiviral with demonstrated in vitro activity against multiple viruses, including severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). This trial evaluated the potential of ribavirin inhalation solution (ribavirin aerosol) to reduce COVID‐19 disease severity in adults with confirmed SARS‐CoV‐2 infection and a diagnosis of respiratory distress. This phase I, multicenter, open‐label, nonrandomized trial was conducted from February 2021 through August 2021. Patients received ribavirin aerosol (100 mg/ml for 30 min or 50 mg/ml for 60 min) twice daily for up to 6 days. The primary end point was change from baseline in clinical status severity, rated on a 7‐point scale (1 [death]; 7 [not hospitalized; no limitations on activities]), at day 7 (or end‐of‐treatment/early termination) and day 30 (follow‐up). Fifty‐one patients were treated with ribavirin aerosol (mean age, 51.5 years; 78.4% men); mean number of doses was 9.7 (range, 1–12). Improvement of ≥1 level in clinical status severity was observed in 31.4% (16/51) and 78.4% (40/51) of patients at end‐of‐treatment and day 30, respectively. Of 21 patients who required a ventilator, 16 (76.2%) were able to discontinue ventilator use. Five patients (9.8%) died between end‐of‐treatment and day 30. Three patients (5.9%) discontinued study treatment due to adverse events. No deaths were considered related to study treatment. These data provide preliminary evidence that ribavirin aerosol may be an efficacious treatment for respiratory distress in adults with COVID‐19.
Complex sweat gland hamartoma: A case report
Authors: Skopec Zachary , Berrebi Kristen G. , Stone Mary , Liu Vincent
Published: November 2022

Syringocystadenoma papilliferum (SCAP), tubular apocrine adenoma (TAA), and eccrine nevus are rare benign sweat gland tumors with varied clinical presentations but generally distinctive histomorphologic profiles. TAA and SCAP have been associated with other cutaneous hamartomas, most commonly with nevus sebaceus. Additionally, TAA and SCAP have uncommonly co‐occurred in the same lesion. In contrast to nevus sebaceus, eccrine nevus is considerably less common and is rarely associated with other benign adnexal lesions. Here we present an unusual case of a complex sweat gland hamartoma containing features of syringocystadenoma papilliferum, tubular apocrine adenoma, and eccrine nevus in a 7‐year‐old female.
Toward the articulation of mission: Heeding the ELCA's call for affordable mental health care and authentic diversity while guiding students' journeys toward counseling and clinical vocations
Authors: Holigrocki Richard
Published: November 2022

I describe community counseling clinics embedded with a Lutheran University and aligned with Evangelical Lutheran Church in America (ELCA) values. Our clinics, like many others, serve the underserved and are often dependent upon external support. To ensure operational stability, they must articulate their mission alignment with host institutions and funders. In so doing, funders readily see how their values are enacted and embodied within the supported program. Examples of mission alignment, data supporting alignment, and the benefits of alignment for the program, funder, and those served are provided.
Cerebellar involvement associated with immune checkpoint inhibitors: A systematic review
Authors: Dinoto Alessandro , Mantovani Elisa , Ferrari Sergio , Mariotto Sara , Tamburin Stefano
Published: November 2022

Background and purpose

Immune checkpoint inhibitors (ICIs) targeting programmed death receptor 1 (PD‐1), cytotoxic T‐lymphocyte‐associated‐4 (CTLA‐4) and programmed cell death ligand 1 can be associated with immune‐related adverse events (iRAEs). Amongst neurological iRAEs, cerebellar involvement seems to be rare and currently lacks a proper characterization. The aim of this study was to phenotype cerebellar iRAEs.

Methods

A systematic review was performed according to PRISMA guidelines including reported patients with cerebellar involvement related to ICIs and with available individual data.

Results

After screening 2765 records, 32 studies with 46 patients were included. Median age was 63 years (20–82), and most patients were male (63.0%). Isolated cerebellitis was observed in 32.6% of cases, whilst the remaining cases had “cerebellitis plus”, mostly associated with encephalitis/encephalopathy. Associated tumors included most frequently lung cancer, melanoma and Merkel cell carcinoma. PD‐1 inhibitor was the most administered treatment (n = 29, 64.4%), whilst exposure to CTLA‐4 inhibitor was rare (n = 2, 4.5%). Magnetic resonance imaging was abnormal in 43.2% of patients and inflammatory cerebrospinal fluid findings were frequently observed. Autoantibodies were detected in 61.9% of patients and included novel reactivities. Amongst treatment strategies, the most common were steroids (n = 36) and ICI discontinuation (n = 28, 90.3%). Relapses were reported in 10% of patients. Most patients showed improvement/remission (n = 31) but, at last follow‐up, 12 had died. Isolated cerebellitis versus cerebellitis‐plus differed in terms of outcomes, whilst seropositive versus seronegative patients had distinct tumor associations.

Discussion

Cerebellar iRAEs are usually multifocal, have heterogeneous tumor associations, are most associated with PD‐1 inhibitor exposure and are related to autoantibodies, including novel reactivities.
Association between subjective cognitive complaints, balance impairment and disability among middle‐aged and older adults: Evidence from a population‐based cohort study
Authors: Tu Raoping , Wang Suhang , He Huihui , Ding Jiali , Zeng Qingping , Guo Lu , Li Yueping , Xu Tianwei , Lu Guangyu
Published: November 2022

Aim

To quantify the association between subjective cognitive complaints and balance impairment in relation to the occurrence of disability.

Methods

In total, 6885 adults aged ≥45 who participated in the China Health and Retirement Longitudinal Study (CHARLS) were followed for 7 years. Subjective cognitive complaints were evaluated by self‐reported memory problems. Balance impairment was tested by side‐by‐side stand, semi‐tandem stand and full tandem stand. Disability was measured by activities of daily living (ADL) and instrumental activities of daily living (IADL). Multivariate logistic regression models were applied to test the joint effect between baseline subjective cognitive complaints and balance impairment on disability. The multiplicative interaction was examined.

Results

A joint effect of experiencing both subjective cognitive complaints and balance impairment was identified, showing a 1.63‐fold higher risk of ADL and IADL disability than those experienced by neither of the two (odds ratio = 1.63, 95% confidence interval: 1.36–1.95). There was evidence of multiplicative interaction (P = 0.004).

Conclusions

Among middle‐aged and older people, the coexistence of subjective cognitive complaints and balance impairment may lead to a higher disability risk, which is much higher than the simple sum of the two individual effects. Future interventions are required to target these symptoms simultaneously to reduce the risks of disability. Geriatr Gerontol Int 2022; 22: 1025–1031.
Effect of different postmortem ageing conditions on physicochemical properties, structure and water‐holding capacity of pork
Authors: Zhang Handan , Cao Yungang , Dong Xinling , Li Xia , Zhang Chunhui
Published: November 2022

This study aimed to determine the effects of postmortem ageing temperatures on protein–water interactions and muscle water‐holding capacity (WHC) of pork. The oxidation degree, solubility and secondary structure of myofibrillar protein (MP) were also studied. Porcine longissimus lumborum muscles were aged at −6 ± 1, 4 ± 1, and 10 ± 1°C for 3, 12, 24, 72, 120 and 168 h, respectively. The results showed the lower ageing temperature is conducive to decrease the protein oxidation and the transformation of protein conformation from ordered structures (α‐helices and β‐sheets) to disordered structures (β‐turns and random coils). These physicochemical changes favoured protein–water interactions, thus the muscle samples aged at −6 ± 1°C for 120 h had the highest protein solubility and WHC. This work revealed that ageing at sub‐freezing temperature (−6 ± 1°C) is beneficial to reduce protein oxidation and improve muscle water‐holding capacity.
Protein hydrolysate from salmon frame debittered by plastein reaction: amino acid composition, characteristics and antioxidant activities
Authors: Sharma Kartik , Nilsuwan Krisana , Zhang Bin , Hong Hui , Benjakul Soottawat
Published: November 2022

Impacts of plastein reaction on bitterness, physicochemical and antioxidant properties of salmon frame hydrolysate with the aid of various proteases (alcalase and papain) at different concentrations and varying reaction temperatures were investigated. Plastein was produced from hydrolysate by papain at 40°C, which had 30% degree of hydrolysis (30DHP). Rearrangement of peptides in hydrolysate was performed by 1% papain at 40°C for 10 h, yielding plastein namely ‘30DHP‐P1’. It showed the lowest bitterness (P < 0.05) than other plasteins and hydrolysates. Surface hydrophobicity was not related well with bitterness. Therefore, the size of peptides also determines the bitterness. 30DHP‐P1 had augmented solubility; however, its antioxidant activities (DPPH and ABTS radical scavenging activities and ferric reducing antioxidant power) were slightly lower (P < 0.05) than those of hydrolysates. Bitterness of hydrolysate was markedly debittered via plastein reaction under optimal condition. Plastein generally had lighter colour and still possessed antioxidant activity.
Clinical in‐situ evaluation of the effect of rubber dam isolation on bond strength to enamel
Authors: Falacho Rui I. , Melo Eliana Azevedo , Marques Joana A. , Ramos João Carlos , Guerra Fernando , Blatz Markus B.
Published: November 2022

Objective

To evaluate the effect of rubber dam isolation on shear bond strength of two different adhesive systems to enamel.

Materials and Methods

The mesial, distal, lingual, and vestibular enamel surfaces of thirty human third molars were prepared (total n = 120). A custom splint was made to fit a volunteer's maxilla, holding the specimens in place in the oral cavity. Four composite resin cylinders were bonded to each tooth with one of two bonding agents (OptiBond FL and Prime&Bond active) with or without rubber dam isolation. Shear bond strength was tested in a universal testing machine and failure modes were assessed. Significance level for statistical analyses was set at 5%.

Results

All pairwise comparisons revealed statistical differences (p < 0.05). The highest mean shear bond strength values were obtained in rubber dam experimental groups, regardless of the adhesive system. Group OptiBond FL with rubber dam presented the highest mean bond strength values. Fracture modes for specimens bonded without rubber dam isolation were adhesive and cohesive within enamel, while rubber dam experimental groups revealed only cohesive fractures.

Conclusions

Absolute isolation with rubber dam increases bond strength to enamel, independent of the adhesive system. The three‐step total‐etch system OptiBond FL provided significantly higher bond strength values than Prime&Bond active under both experimental conditions.

Clinical Significance

Rubber dam isolation has a significant effect on bond strengths to enamel, independent of the adhesive system. Its application is, therefore, advised whenever adhesive procedures are performed. A filled three‐step etch‐and‐rinse adhesive performed superiorly, with or without rubber dam isolation, when bonding to enamel compared to an isopropanol‐based universal adhesive.
Distinct phenotypic clusters of sleep‐disordered breathing and their association with medical care‐seeking behaviour and sleep habits: the Guangdong Sleep Health Study
Authors: Wang Longlong , Ou Qiong , Shan Guangliang , Lao Miaochan , Xu Yanxia , Pei Guo
Published: November 2022

Sleep‐disordered breathing (SDB) is highly prevalent, but its rates of diagnosis and treatment are low. As a heterogeneous condition, it is associated with delayed diagnosis and/or suboptimal treatment. We aimed to determine distinct SDB clusters and examine their association with medical care‐seeking behaviour and sleep habits in a community‐dwelling population in South China. Participants were enrolled in the ‘Guangdong Sleep Health Study’. Five distinct community sites were investigated. Participant information was collected, and overnight sleep monitoring was performed. Latent class analysis was performed to classify patients with SDB based on patterns of SDB‐related symptoms and signs. Overall, 1,524 patients with SDB were evaluated. Four distinct clusters were identified: ‘minimally symptomatic’ (Cluster 2), which was the most dominant subtype (41.6%), followed by ‘pure insomnia/fewer daytime symptoms’ (Cluster 4; 24.7%), ‘insomnia/multiple daytime symptoms’ (Cluster 3; 17.8%), and ‘upper airway symptoms with sleepiness’ (Cluster 1; 15.9%). The overall medical care‐seeking rate attributable to sleep and breathing disorders was only 3.3%: 10.3% in Cluster 3, 2.5% in Cluster 1, 2.1% in Cluster 4, and 1.3% in Cluster 2, in which Cluster 3 was the highest and Cluster 2 was the lowest (adjusted p < 0.05). Regarding the sleep habit of going to bed and waking up at a consistent time, Cluster 3 exhibited the worst performance and Cluster 2 the best. In conclusion, distinct phenotypic subtypes were identified in community‐dwelling patients with SDB. Tailored strategies to encourage medical care‐seeking, early identification, and optimisation of treatment are necessary considering the different subtypes.
Rapid sleep education: If you could tell people one thing about sleep, what should it be?
Authors: Barley Blake K. , Walter Charles , Orselli Paul , Scullin Michael K.
Published: November 2022

Informal learning settings such as museums provide unique opportunities for educating a local community about sleep. However, in such settings, information must be capable of immediately inciting interest. We developed a series of sleep “icebreakers” (brief, informal facts) to determine whether they elicited interest in sleep and encouraged behavioural change. There were 859 participants across three cross‐sectional samples: (a) members of the local museum; (b) Mechanical Turk workers who responded to a “sleep” study advertisement; and (c) Mechanical Turk workers who responded to a “various topics” study advertisement that did not mention sleep. All three samples demonstrated high interest in sleep topics, though delayed recall of the icebreakers was strongest in participants who expected to learn about the sleep topics. Icebreaker interest ratings were independent of age, gender and race/ethnicity, suggesting that sleep is a topic of universal interest. Importantly, regardless of demographics and sample, the more the icebreakers interested the participants, the more likely participants were to indicate willingness to donate to a sleep exhibit, change their sleep behaviours, and post to social media. Thus, sleep icebreakers can rapidly elicit people's interest, and future outreach efforts should couple icebreakers with opportunities for subsequent personalized learning.
Disease burden in primary sclerosing cholangitis in the Netherlands: A long‐term follow‐up study
Authors: van Munster Kim N. , Mol Bregje , Goet Jorn C. , van Munster Sanne N. , Weersma Rinse K. , de Vries Annemarie C. , van der Meer Adriaan J. , Inderson Akin , Drenth Joost P. , van Erpecum Karel J. , Boonstra Kirsten , Beuers Ulrich , Dijkgraaf Marcel G. W. , Ponsioen Cyriel Y. ,   the EpiPSC2 Study Group
Published: November 2022

Background & Aims

Primary sclerosing cholangitis (PSC) is a progressive, cholestatic liver disease which greatly impacts the lives of individuals. Burden of disease due to shortened life expectancy and impaired quality of life is ill‐described. The aim of this study was to assess long‐term disease burden in a large population‐based registry with regard to survival, clinical course, quality adjusted life years (QALYs), medical consumption and work productivity loss.

Methods

All PSC patients living in a geographically defined area covering ~50% of the Netherlands were included, together with patients from the three liver transplant centres. Survival was estimated by competing risk analysis. Proportional shortfall of QALYs during disease course was measured relative to a matched reference cohort using validated questionnaires. Work productivity loss and medical consumption were evaluated over time.

Results

A total of 1208 patients were included with a median follow‐up of 11.2 year. Median liver transplant‐free survival was 21.0 years. Proportional shortfall of QALYs increased to 48% >25 years after diagnosis. Patients had on average 12.4 hospital contact days among which 3.17 admission days per year, annual medical costs were €12 169 and mean work productivity loss was 25%.

Conclusions

Our data quantify for the first time disease burden in terms of QALYs lost, clinical events, medical consumption, costs as well as work productivity loss, and show that all these are substantial and increase over time.
Genomic and phenotypic changes associated with alterations of migratory behaviour in a songbird
Authors: Zhang Dezhi , She Huishang , Rheindt Frank E. , Wu Lei , Wang Huan , Zhang Kai , Cheng Yalin , Song Gang , Jia Chenxi , Qu Yanhua , Olsson Urban , Alström Per , Lei Fumin
Published: November 2022

The seasonal migration of birds is a fascinating natural wonder. Avian migratory behaviour changes are common and are probably a polygenic process as avian migration is governed by multiple correlated components with a variable genetic basis. However, the genetic and phenotypic changes involving migration changes are poorly studied. Using one annotated near‐chromosomal level de novo genome assembly, 50 resequenced genomes, hundreds of morphometric data and species distribution information, we investigated population structure and genomic and phenotypic differences associated with differences in migratory behaviour in a songbird species, Yellow‐throated BuntingEmberiza elegans(Aves: Emberizidae). Population genomic analyses reveal extensive gene flow between the southern resident and the northern migratory populations of this species. The hand‐wing index is significantly lower in the resident populations than in the migratory populations, indicating reduced flight efficiency of the resident populations. Here, we discuss the possibility that nonmigratory populations may have originated from migratory populations though migration loss. We further infer that the alterations of genes related to energy metabolism, nervous system and circadian rhythm may have played major roles in regulating migration change. Our study sheds light on phenotypic and polygenic changes involving migration change.
Insights into symbiotic interactions from metatranscriptome analysis of deep‐sea mussel Gigantidas platifrons under long‐term laboratory maintenance
Authors: Sun Yan , Wang Minxiao , Chen Hao , Wang Hao , Zhong Zhaoshan , Zhou Li , Fu Lulu , Li Chaolun , Sun Song
Published: November 2022

Symbioses between invertebrates and chemosynthetic bacteria are of fundamental importance in deep‐sea ecosystems, but the mechanisms that enable their symbiont associations are still largely undescribed, owing to the culturable difficulties of deep‐sea lives. Bathymodiolinae mussels are remarkable in their ability to overcome decompression and can be maintained successfully for an extended period under atmospheric pressure, thus providing a model for investigating the molecular basis of symbiotic interactions. Herein, we conducted metatranscriptome sequencing and gene co‐expression network analysis of Gigantidas platifrons under laboratory maintenance with gradual loss of symbionts. The results revealed that one‐day short‐term maintenance triggered global transcriptional perturbation in symbionts, but little gene expression changes in mussel hosts, which were mainly involved in responses to environmental changes. Long‐term maintenance with depleted symbionts induced a metabolic shift in the mussel host. The most notable changes were the suppression of sterol biosynthesis and the complementary activation of terpenoid backbone synthesis in response to the reduction of bacteria‐derived terpenoid sources. In addition, we detected the upregulation of host proteasomes responsible for amino acid deprivation caused by symbiont depletion. Additionally, a significant correlation between host microtubule motor activity and symbiont abundance was revealed, suggesting the possible function of microtubule‐based intracellular trafficking in the nutritional interaction of symbiosis. Overall, by analyzing the dynamic transcriptomic changes during the loss of symbionts, our study highlights the nutritional importance of symbionts in supplementing terpenoid compounds and essential amino acids and provides insight into the molecular mechanisms and strategies underlying the symbiotic interactions in deep‐sea ecosystems.
Simultaneous editing of three homoeologues of TaCIPK14 confers broad‐spectrum resistance to stripe rust in wheat
Authors: He Fuxin , Wang Ce , Sun Huilin , Tian Shuxin , Zhao Guosen , Liu Cong , Wan Cuiping , Guo Jia , Huang Xueling , Zhan Gangming , Yu Xiumei , Kang Zhensheng , Guo Jun
Published: November 2022

Wheat stripe rust caused by the fungus Puccinia striiformis f. sp. tritici (Pst) is one of the most destructive wheat diseases resulting in significant losses to wheat production worldwide. The development of disease‐resistant varieties is the most economical and effective measure to control diseases. Altering the susceptibility genes that promote pathogen compatibility via CRISPR/Cas9‐mediated gene editing technology has become a new strategy for developing disease‐resistant wheat varieties. Calcineurin B‐like protein (CBL)‐interacting protein kinases (CIPKs) has been demonstrated to be involved in defence responses during plant‐pathogen interactions. However, whether wheat CIPK functions as susceptibility factor is still unclear. Here, we isolated a CIPK homoeologue gene TaCIPK14 from wheat. Knockdown of TaCIPK14 significantly increased wheat resistance to Pst, whereas overexpression of TaCIPK14 resulted in enhanced wheat susceptibility to Pst by decreasing different aspects of the defence response, including accumulation of ROS and expression of pathogenesis‐relative genes. We generated wheat Tacipk14 mutant plants by simultaneous modification of the three homoeologues of wheat TaCIPK14 via CRISPR/Cas9 technology. The Tacipk14 mutant lines expressed race‐nonspecific (RNS) broad‐spectrum resistance (BSR) to Pst. Moreover, no significant difference was found in agronomic yield traits between Tacipk14 mutant plants and Fielder control plants under greenhouse and field conditions. These results demonstrate that TaCIPK14 acts as an important susceptibility factor in wheat response to Pst, and knockout of TaCIPK14 represents a powerful strategy for generating new disease‐resistant wheat varieties with BSR to Pst.
Seed priming with brassinolides improves growth and reinforces antioxidative defenses under normal and heat stress conditions in seedlings of Brassica juncea
Authors: Neha  , Twinkle  , Mohapatra Sumanta , Sirhindi Geetika , Dogra Vivek
Published: November 2022

Environmental stresses pose a major challenge for plant researchers to fulfill increasing food demand. Researchers are trying to generate high‐yielding and stress‐tolerant or resistant varieties using classical genetics and modern gene‐editing tools; however, both approaches have limitations. Chemical treatments emerged as an alternative to improve yield and impart stress resilience. Brassinosteroids (BRs) are a group of phytohormones that regulate various biological processes, including stress management. With foliar spray methods, BR treatments showed promising results but are not economically feasible. We hypothesize that priming of seeds, which requires lesser amounts of BRs, could be equally effective in promoting growth and stress tolerance. Owing to this notion, we analyzed the impact of priming seeds with selected BRs, namely, 24‐epibrassinolide (EBL) and 28‐homobrassinolide (HBL), in Brassica juncea under normal and heat shock stress conditions. Seeds primed with BRs and grown until seedlings stage at normal conditions (20°C) were subjected to a heat shock (35°C) for a few hours, relating to what plants experience in natural conditions. Heat shock reduced the growth and biomass with an increased accumulation of reactive oxygen species. As anticipated, BRs treatments significantly improved the growth and physiological parameters with an enhanced antioxidant defense under both conditions. Transcriptional analyses revealed that BRs concomitantly induce growth and oxidative stress‐responsive gene expression via the canonical BR‐signaling pathway. Transfer of unstressed and heat‐shock‐treated seedlings to field conditions demonstrated the long‐term effectivity of BR‐priming. Our results showed seed priming with BRs could improve growth and resilience against heat shock; hence, it appears to be a viable strategy to enhance crop yields and stress tolerance.
“Protect the women!” Trans‐exclusionary feminist issue framing and support for transgender rights
Authors: Turnbull‐Dugarte Stuart J. , McMillan Fraser
Published: November 2022

An increasingly salient policy innovation pursued by LGBT+ rights groups and socially liberal policy entrepreneurs is the right of trans people to bring their legally recorded sex in line with their lived gender by way of self‐identification. In response to these moves toward trans inclusion, a unique coalition of trans‐exclusionary (gender critical) feminists and traditionalist conservatives has emerged to challenge these reforms. This coalition of policy opponents, mirroring historical issue frames that present homosexuals as predatory sexual deviants, campaign on a salient issue frame that presents transgender individuals and the expansion of trans rights as an inimical threat to the security, safety, and welfare of (cisgender) women, particularly in single‐sex spaces. In this paper, we address two questions. First, we ask: do trans‐exclusionary “protect women” issue frames over the alleged threat of trans persons to (cis) women shape mass public opinion? Second, we ask: in a relatively LGBT+ friendly policy environment, who supports the right to self‐identification for trans individuals? We answer these questions via an original pre‐registered survey experiment embedded within the 2021 Scottish Election Study. We find that trans‐exclusionary issue frames appealing to (cis) women's safety significantly depress support for trans rights, particularly among women respondents. Highlighting these concerns is an effective means of increasing already robust opposition to reforms designed to improve the welfare of transgender individuals, which should be of concern for proponents of self‐identification policies.
Individualized prediction of trait self‐control from whole‐brain functional connectivity
Authors: Ren Zhiting , Sun Jiangzhou , Liu Cheng , Li Xinyue , Li Xianrui , Li Xinyi , Liu Zeqing , Bi Taiyong , Qiu Jiang
Published: November 2022

Self‐control is a core psychological construct for human beings and it plays a crucial role in the adaptation to society and achievement of success and happiness for individuals. Although progress has been made in behavioral studies examining self‐control, its neural mechanisms remain unclear. In this study, we employed a machine‐learning approach—relevance vector regression (RVR) to explore the potential predictive power of intrinsic functional connections to trait self‐control in a large sample (N = 390). We used resting‐state functional MRI (fMRI) to explore whole‐brain functional connectivity patterns characteristic of 390 healthy adults and to confirm the effectiveness of RVR in predicting individual trait self‐control scores. A set of connections across multiple neural networks that significantly predicted individual differences were identified, including the classic control network (e.g., fronto‐parietal network (FPN), salience network (SAL)), the sensorimotor network (Mot), and the medial frontal network (MF). Key nodes that contributed to the predictive model included the dorsolateral prefrontal cortex (dlPFC), middle frontal gyrus (MFG), anterior cingulate and paracingulate gyri, inferior temporal gyrus (ITG) that have been associated with trait self‐control. Our findings further assert that self‐control is a multidimensional construct rooted in the interactions between multiple neural networks.
Rethinking ‘immunological memory’: Local and systemic immunity provided by bone marrow‐resident memory cells
Authors: McGrath Mairi Anne , Dong Jun , Mashreghi Mir‐Farzin , Chang Hyun‐Dong , Radbruch Andreas
Published: November 2022

It has been 25 years since we first described long‐lived memory plasma cells of the bone marrow, 13 years since we identified bone marrow resident memory T cells and 2 years since we showed that the bone marrow is also a preferred location of resident memory B cells. The bone marrow is increasingly recognized as a fundamental component of long‐lasting immunological memory, not only providing protective immunity but also fuelling chronic inflammation. We now understand that the bone marrow functions as the ‘backbone’ of immunological memory, hosting the memory plasma cells which provide not only humoral immunity but also memory B and T cells, which constitute ‘reactive memory’. This knowledge now allows us to define true cellular ‘correlates of protection’ for systemic immunity, its quality and duration, as induced by infection and vaccination, something that has never been more important given the recent SARS‐CoV‐2 pandemic. While memory plasma cells of the bone marrow indicate long‐lasting humoral protection, memory T (and B) cells mobilized into the blood in secondary immune reactions indicate the strength of reactive memory. In this review, we have contextualized many of our own findings from the last two decades that have contributed to our understanding of how bone marrow‐resident memory cells provide local and systemic immunity.
Longitudinal association of sedentary time and physical activity with pain and quality of life in fibromyalgia
Authors: Gavilán‐Carrera Blanca , Delgado‐Fernández Manuel , Álvarez‐Gallardo Inmaculada C. , Acosta‐Manzano Pedro , Borges‐Cosic Milkana , Estévez‐López Fernando , Soriano‐Maldonado Alberto , Carbonell‐Baeza Ana , Aparicio Virginia A. , Segura‐Jiménez Víctor
Published: November 2022

Objective

To analyze changes over time and the predictive value of baseline and changes of sedentary time (ST) and physical activity (PA) on pain, disease impact, and health‐related quality of life (HRQoL) at 2‐ and 5‐year follow‐up in women with fibromyalgia.

Methods

This is a longitudinal and exploratory study with three time points. A total of 427 women with fibromyalgia (51.4 ± 7.6 years) were followed after 2 (n = 172) and 5 years (n = 185). ST and PA (light and moderate‐to‐vigorous [MVPA]) were assessed using triaxial accelerometers. Pain, disease impact, and HRQoL were measured using: pressure pain threshold, the pain subscale of the revised fibromyalgia impact questionnaire (FIQR), the bodily pain subscale of the 36‐item short‐form health survey (SF‐36), a visual analog scale (VAS), the FIQR, and the SF‐36 physical and mental components.

Results

Over 5 years, pressure pain threshold, ST, light PA, and MVPA variables were worsened, while FIQR and SF‐36 variables were improved (Cohen's d < 0.1–0.3). Baseline ST or light PA were not associated with future outcomes, whereas greater MVPA at baseline was associated with better SF‐36 bodily pain at 5‐year follow‐up (β = 0.13). Reducing ST and increasing light PA were associated with better bodily pain (β = −0.16 and 0.17, respectively) and SF‐36 physical component (β = −0.20 and 0.17, respectively) at 5‐year follow‐up. Increasing MVPA was associated with less pain (pressure pain threshold, VAS, and FIQR‐pain) and better SF‐36 physical component at 2‐ and 5‐year follow‐up (β's from −0.20 to 0.21).

Conclusions

Objectively measured variables slightly worsened over years, while for self‐reported outcomes there was a trend for improvement. Reductions in ST and increases in light PA and MVPA were associated with better HRQoL at 5‐year follow‐up, and increases in MVPA were additionally associated with better pain and HRQoL at 2‐year follow‐up.
Organic Rankine Cycle Turbine and Heat Exchanger Sizing for Liquid Air Combined Cycle
Authors: Pryor Owen , Rimpel Aaron , Conlon William
Published: November 2022

Cryogenic energy storage offers several opportunities to design turbomachinery and other equipment for novel cycles. This paper presents the design and analysis of turbomachinery and heat exchangers for an Organic Rankine Cycle (ORC) subsystem for a hybrid energy storage concept. The Liquid Air Combined Cycle is an energy storage system that stores air at cryogenic conditions at times with high variable renewable energy to be dispatched along with a gas turbine to recover the exhaust heat. In order to re-vaporize the air, the liquid air is coupled with an ORC as an additional bottoming cycle. The ORC turbine is expected to expand the fluid with a pressure ratio of nearly 30 and a flow rate of approximately 45 kg/s. Sizing calculations for both a radial and axial turbine solution were performed over a range of speeds and stages to determine the optimal design point. The results show that either an axial (8- or 9-stage) or radial (four stages at two shaft speeds) turbine are capable of handling the pressure ratios. Further trades of the two configurations would be required to determine the best option. The ORC system also incorporates five heat exchangers to distribute heat, vaporize the liquid air, or recover exhaust heat from the gas turbine. Three heat exchangers were analyzed to understand the size of heat exchangers and pressure drop for the overall system. Different types of heat exchangers were explored for the different purposes, including plate-fin heat exchangers, gasketed plate heat exchangers and shell-in-tube heat exchangers. It was determined that the ORC recuperator, liquid-air vaporizer, and vaporized air pre-heater would be counter-flow heat exchangers using a gasketed plate design.
Amblyseius herbicolus mothers prefer to oviposit near eggs of non-kin in the absence of prey Carpoglyphus lactis (Acari: Phytoseiidae, Carpoglyphidae)
Authors: Zhang Keshi , Zhang Zhi-Qiang
Published: November 2022

Many animal species can recognise and discriminate conspecifics differing in their genetic relatedness. The discrimination of kin from non-kin or more distantly related kin can benefit individuals with increased inclusive fitness and avoid adverse influences from inbreeding. A preference by mothers to oviposit near their own or closely related eggs rather than ovipositing near non-kin or distantly related eggs has been observed in several phytoseiids, possibly to reduce cannibalism and allow imprinting between siblings. The phytoseiid Amblyseius herbicolus reluctantly cannibalise kin (i.e. siblings or offspring) in the presence of non-kin or more distantly related kin. This study investigated the oviposition preference of A. herbicolus females when provided with two sites, each containing either their own eggs or eggs laid by non-kin. The influence of food on such oviposition site preference is largely unknown in phytoseiids. Thus, we also examined the oviposition site choice of A. herbicolus females in the presence and absence of its prey Carpoglyphus lactis eggs. Our results demonstrated a significant influence of prey on the oviposition site preference of A. herbicolus: adults preferred to oviposit near eggs of non-kin in the absence of prey but showed no preference when C. lactis eggs were present at both sites. We suggest that A. herbicolus females preferred to oviposit near eggs of non-kin in the absence of prey to possibly avoid kin cannibalism during food stress.
The emergent properties of the connected brain
Authors: Thiebaut de Schotten Michel , Forkel Stephanie J.
Published: November 2022

There is more to brain connections than the mere transfer of signals between brain regions. Behavior and cognition emerge through cortical area interaction. This requires integration between local and distant areas orchestrated by densely connected networks. Brain connections determine the brain’s functional organization. The imaging of connections in the living brain has provided an opportunity to identify the driving factors behind the neurobiology of cognition. Connectivity differences between species and among humans have furthered the understanding of brain evolution and of diverging cognitive profiles. Brain pathologies amplify this variability through disconnections and, consequently, the disintegration of cognitive functions. The prediction of long-term symptoms is now preferentially based on brain disconnections. This paradigm shift will reshape our brain maps and challenge current brain models.
Molecular basis of astrocyte diversity and morphology across the CNS in health and disease
Authors: Endo Fumito , Kasai Atsushi , Soto Joselyn S. , Yu Xinzhu , Qu Zhe , Hashimoto Hitoshi , Gradinaru Viviana , Kawaguchi Riki , Khakh Baljit S.
Published: November 2022

Astrocytes, a type of glia, are abundant and morphologically complex cells. Here, we report astrocyte molecular profiles, diversity, and morphology across the mouse central nervous system (CNS). We identified shared and region-specific astrocytic genes and functions and explored the cellular origins of their regional diversity. We identified gene networks correlated with astrocyte morphology, several of which unexpectedly contained Alzheimer’s disease (AD) risk genes. CRISPR/Cas9–mediated reduction of candidate genes reduced astrocyte morphological complexity and resulted in cognitive deficits. The same genes were down-regulated in human AD, in an AD mouse model that displayed reduced astrocyte morphology, and in other human brain disorders. We thus provide comprehensive molecular data on astrocyte diversity and mechanisms across the CNS and on the molecular basis of astrocyte morphology in health and disease.
Polarized x-rays constrain the disk-jet geometry in the black hole x-ray binary Cygnus X-1
Authors: Krawczynski Henric , Muleri Fabio , Dovčiak Michal , Veledina Alexandra , Rodriguez Cavero Nicole , Svoboda Jiri , Ingram Adam , Matt Giorgio , Garcia Javier A. , Loktev Vladislav , Negro Michela , Poutanen Juri , Kitaguchi Takao , Podgorný Jakub , Rankin John , Zhang Wenda , Berdyugin Andrei , Berdyugina Svetlana V. , Bianchi Stefano , Blinov Dmitry , Capitanio Fiamma , Di Lalla Niccolò , Draghis Paul , Fabiani Sergio , Kagitani Masato , Kravtsov Vadim , Kiehlmann Sebastian , Latronico Luca , Lutovinov Alexander A. , Mandarakas Nikos , Marin Frédéric , Marinucci Andrea , Miller Jon M. , Mizuno Tsunefumi , Molkov Sergey V. , Omodei Nicola , Petrucci Pierre-Olivier , Ratheesh Ajay , Sakanoi Takeshi , Semena Andrei N. , Skalidis Raphael , Soffitta Paolo , Tennant Allyn F. , Thalhammer Phillipp , Tombesi Francesco , Weisskopf Martin C. , Wilms Joern , Zhang Sixuan , Agudo Iván , Antonelli Lucio A. , Bachetti Matteo , Baldini Luca , Baumgartner Wayne H. , Bellazzini Ronaldo , Bongiorno Stephen D. , Bonino Raffaella , Brez Alessandro , Bucciantini Niccolò , Castellano Simone , Cavazzuti Elisabetta , Ciprini Stefano , Costa Enrico , De Rosa Alessandra , Del Monte Ettore , Di Gesu Laura , Di Marco Alessandro , Donnarumma Immacolata , Doroshenko Victor , Ehlert Steven R. , Enoto Teruaki , Evangelista Yuri , Ferrazzoli Riccardo , Gunji Shuichi , Hayashida Kiyoshi , Heyl Jeremy , Iwakiri Wataru , Jorstad Svetlana G. , Karas Vladimir , Kolodziejczak Jeffery J. , La Monaca Fabio , Liodakis Ioannis , Maldera Simone , Manfreda Alberto , Marscher Alan P. , Marshall Herman L. , Mitsuishi Ikuyuki , Ng Chi-Yung , O’Dell Stephen L. , Oppedisano Chiara , Papitto Alessandro , Pavlov George G. , Peirson Abel L. , Perri Matteo , Pesce-Rollins Melissa , Pilia Maura , Possenti Andrea , Puccetti Simonetta , Ramsey Brian D. , Romani Roger W. , Sgrò Carmelo , Slane Patrick , Spandre Gloria , Tamagawa Toru , Tavecchio Fabrizio , Taverna Roberto , Tawara Yuzuru , Thomas Nicholas E. , Trois Alessio , Tsygankov Sergey , Turolla Roberto , Vink Jacco , Wu Kinwah , Xie Fei , Zane Silvia
Published: November 2022

A black hole x-ray binary (XRB) system forms when gas is stripped from a normal star and accretes onto a black hole, which heats the gas sufficiently to emit x-rays. We report a polarimetric observation of the XRB Cygnus X-1 using the Imaging X-ray Polarimetry Explorer. The electric field position angle aligns with the outflowing jet, indicating that the jet is launched from the inner x-ray–emitting region. The polarization degree is 4.01 ± 0.20% at 2 to 8 kiloelectronvolts, implying that the accretion disk is viewed closer to edge-on than the binary orbit. These observations reveal that hot x-ray–emitting plasma is spatially extended in a plane perpendicular to, not parallel to, the jet axis.