bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequencing and characterization of Helcococcus ovis: a comprehensive comparative genomic analysis of virulence
Authors: Cunha Federico , Casaro Segundo , Jones Kristi L. , Bisinotto Rafael S. , Kariyawasam Subhashinie , Brown Mary B. , Galvão Klibs N.
Published: August 2023

Background

Helcococcus ovis (H. ovis) is an emerging bacterial pathogen that commonly causes opportunistic respiratory, mammary, and uterine infections across mammalian hosts. This study applied long- and short-read whole genome sequencing technologies to identify virulence factors in five H. ovis isolates with low, medium, and high virulence phenotypes.

Results

The resulting assemblies contained one circular chromosome ranging from 1,744,566 to 1,850,083 bp in length and had a mean GC content of 27.6%. Phylogenetic and nucleotide identity analyses found low virulence strain KG38 to be part of a clade that forms an outgroup apart from the rest of the H. ovis taxon. Assembling the first complete genomes of the species revealed major genomic rearrangements in KG38. One to six prophage regions were identified in each genome. A novel pathogenicity island was found exclusively in the two high virulence strains (KG37 and KG104), along with two hypothetical transmembrane proteins designated as putative VFs. Finally, three zinc ABC transporters and three Type-II/IV secretion systems were identified as possible virulence determinants in this species. The low virulence strain KG38 has fewer intact paralogs of these operons in its genome compared to the higher virulence isolates, which strongly suggests a role in virulence. This strain is also missing four putative virulence factors (VFs) found in other isolates associated with adherence (collagen adhesin precursor), immune evasion (choline-binding protein A and a PspA-like hypothetical protein) and cell wall synthesis (glycerol-3-phosphate cytidylyltransferase).

Conclusions

In this study, we assembled reference-quality complete genomes for five H. ovis strains to identify putative virulence factors. Phylogenetic analyses of H. ovis isolates revealed the presence of a clade representing a potentially novel species within the genus Helcococcus. A novel pathogenicity island and two hypothetical transmembrane proteins were found exclusively in high-virulence strains. The identification of Zinc ABC transporters and Type-II/IV secretion systems as possible virulence determinants, along with the differences in operon content between the low and high virulence isolates, strongly suggests they also play a role in the bacterium’s pathogenicity. Taken together, these findings are a valuable first step toward deciphering the pathogenesis of H. ovis infections.
Genomic and metabonomic methods reveal the probiotic functions of swine-derived Ligilactobacillus salivarius
Authors: Yang Jiajun , Shang Peng , Zhang Bo , Wang Jing , Du Zhenyu , Wang Shanfeng , Xing Jun , Zhang Hao
Published: August 2023

Background

As substitutes for antibiotics, probiotic bacteria protect against digestive infections caused by pathogenic bacteria. Ligilactobacillus salivarius is a species of native lactobacillus found in both humans and animals. Herein, a swine-derived Ligilactobacillus salivarius was isolated and shown to colonize the ileal mucous membrane, thereby promoting nutritional digestion, absorption, and immunity. To evaluate its probiotic role, the entire genome was sequenced, the genetic information was annotated, and the metabolic information was analyzed.

Results

The phylogenetic relationship indicated that the bacteria was closer to L. salivarius MT573555.1 and MT585431.1. Functional genes included transporters, membrane proteins, enzymes, heavy metal resistance proteins, and putative proteins; metabolism-related genes were the most abundant. The six types of metabolic pathways secreted by L. salivarius were mainly composed of secretory transmembrane proteins and peptides. The secretory proteins of L. salivarius were digestive enzymes, functional proteins that regulate apoptosis, antibodies, and hormones. Non-targeted metabolomic analysis of L. salivarius metabolites suggested that ceramide, pyrrolidone- 5- carboxylic acid, N2-acetyl-L-ornithine, 2-ethyl-2-hydroxybutyric acid, N-lactoyl-phenylalanine, and 12 others were involved in antioxidation, repair of the cellular membrane, anticonvulsant, hypnosis, and appetite inhibition. Metabolites of clavaminic acid, antibiotic X14889C, and five other types of bacteriocins were identified, namely phenyllactic acid, janthitrem G, 13-demethyl tacrolimus, medinoside E, and tertonasin. The adherence and antioxidation of L. salivarius were also predicted. No virulence genes were found.

Conclusion

The main probiotic properties of L. salivarius were identified using genomic, metabonomic, and biochemical assays, which are beneficial for porcine feeding. Our results provided deeper insights into the probiotic effects of L. salivarius.
Effect of preoperative oral rehydration before cesarean section on ultrasound assessment of gastric volume and intraoperative hemodynamic changes: a randomized controlled trial
Authors: Ijiri Eriko , Mori Chie , Sasakawa Tomoki
Published: August 2023

Background

Cesarean section often requires an urgent transfusion load due to decreased blood pressure after spinal anesthesia. This prospective randomized study aimed to investigate whether a preoperative oral rehydration solution (ORS) stabilized perioperative circulatory dynamics.

Methods

Sixty-three parturients scheduled for cesarean section under combined spinal epidural anesthesia (CSEA) were randomly allocated to one of three groups: Group O received 500 mL ORS before bedtime and 500 mL 2 h before CSEA; Group M received mineral water instead of ORS; and Group C had no fluid intake (controls). After entering the operating room, stomach size was measured using ultrasound. Blood samples were obtained, and CSEA was induced. Vasopressors were administered when systolic blood pressure was < 90 mmHg or decreased by > 20%. As a vasopressor, phenylephrine (0.1 mg) was administered at ≥ 60 beats/min heart rate or ephedrine (5 mg) at < 60 beats/min heart rate. The primary outcome was the total number of vasopressor boluses administered. Secondary outcomes were the cross-sectional area of the stomach antrum, maternal plasma glucose levels, serum sodium levels, total intravenous fluid, bleeding volume, urine volume, operative time, and cord blood gas values after delivery.

Results

The total number of vasopressor boluses was lower in Group O than in Group C (P < 0.05). Group O had lower total dose of phenylephrine than Group C (P < 0.05). There were no significant differences between Group M and other groups. No differences were detected regarding secondary outcomes.

Conclusions

In women scheduled for cesarean section, preoperative ORS stabilized perioperative circulatory dynamics. Neither ORS nor mineral water consumption increased the stomach content volume.

Trial Registration

This trial is registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000019825: Date of registration 17/11/2015).
Aortic sinus aneurysm invading ventricular septum and dissection caused by Behcet’s disease: a case report and literature review
Authors: Wu Pengjia , Yu Shaomei , Zeng Jiashun , Yang Lei
Published: August 2023

Few case reports have mentioned the aortic sinus aneurysm invading ventricular septum and dissection caused by Behcet’s disease. Here, we reported a 36-year-old male patient with an aortic sinus aneurysm invading the ventricular septum and dissection caused by Behcet’s disease, who manifested as recurrent chest tightness and shortness of breath. Cardiac ultrasound showed the rupture of the right aortic sinus and the formation of ventricular septal dissection. Ascending aortic valve prosthesis replacement, mitral valvuloplasty with ring implantation and tricuspid valvuloplasty were performed. Postoperatively, he was treated with hormones, hydroxychloroquine sulfate, mycophenolate mofetil tablets, thalidomide and warfarin, and his symptoms were relieved. This is a rare case easily being misdiagnosed and missed, early diagnosis and in-time treatment are crucial to avoid surgical complications. The diagnostic and therapeutic approaches of this patient were reported and related literature was reviewed in this case report.
The trend of change in the role of pre-hospital emergency medical services in Iran’s healthcare system: a situational analysis
Authors: Miri Kheizaran , Sabbaghi Mohammadreza , Mazlum Seyyed Reza , Namazinia Mohammad
Published: August 2023

Introduction

Following the significant changes in healthcare systems over the last century, the role of pre-hospital emergency medical services (EMS) has been drawn against numerous challenges. In view of this, the present study aims to reflect on the trend of change in the role of pre-hospital EMS to meet new situations and needs, thereby providing a clear picture of this process.

Methods

Respecting the intricate concept of development and the major changes in Iran’s healthcare system, this study was fulfilled using situational analysis (SA), developed by Clarke (2018), in Iran within 2022–2023. For this purpose, the data were collected through semi-structured, in-depth individual interviews with four faculty members, two managers involved in EMS, and six highly skilled EMS personnel in various positions. Moreover, the relevant articles published from 1950 to 2023 were reviewed. The data analysis was then performed via SA in the form of open coding as well as simultaneous analysis through three types of maps, viz., situational, social worlds/arenas, and positional maps, along with constant comparative analysis.

Results

Pre-hospital EMS in Iran has thus far had two turning points from 1970 to 2023, wherein academic components, need for equipment and resources, in conjunction with basic needs in the modern society, have been the main propellers. As well, the complexity of care for non-communicable diseases (NCDs), demand for managed care, and technological advancement has gradually resulted in further development in EMS. This trend describes the EMS situation in Iran from 1973 to 2023, as well as the EMS emergence stages, quantitative growth and infrastructure, and clinical education development in 2002–2023, indicating the lack of funding and inadequate scientific infrastructure in proportion to the population receiving such services.

Conclusion

Considering the trend of change in the approaches adopted by healthcare systems across the world, and given the breakthroughs in nursing and medicine, along the education of professionals during the last thirty years, the descriptions of duties and performance in EMS have moved from primary care and patient transfer to specialized services and outpatient care. In addition, the cultural context specific to Iran, the challenges of women working in EMS centers, the disconnection of service providers, namely, the Iranian Red Crescent Society (IRCS) Relief and Rescue Organization (R&RO), Iran’s National Police Force (INPF), and Iran’s National Medical Emergency Organization (INMEO), as well as lack of resources and equipment, and the geographical distribution of human resources (HRs) based on population dispersion, are thus among the significant issues facing pre-hospital EMS in this country.
Healthcare use and clinical investigations before a diagnosis of ovarian cancer: a register-based study in Denmark
Authors: Rousing Isabella Gringer , Vedsted Peter , Hjertholm Peter , Kallestrup Per , Baun Marie-Louise Ladegaard , Virgilsen Line Flytkjaer
Published: August 2023

Background

Ovarian cancer (OC) is associated with a poor prognosis, which calls for earlier diagnosis. This study aimed to analyse the health care use in primary care and at hospitals among women with OC compared to non-cancerous women to identify a window of opportunity for earlier diagnosis.

Methods

This nationwide register-based observational cohort study included all Danish women aged ≥ 40 years who were diagnosed with a first-time OC or borderline ovarian tumour in 2012–2018 and with no previous cancer diagnosis (n = 4,255). For each case, ten non-cancerous women were identified (n = 42,550). We estimated monthly incidence rate ratios using a negative binomial regression model to assess the use of health care services. We calculated risk ratios of having multiple contacts to general practice before a diagnosis using a binary regression model.

Results

Cases had statistically significantly higher contact rates to general practice from five months prior to the diagnosis compared to references. From six to eight months prior to diagnosis, an increased use of transvaginal ultrasound and gynaecologist was seen for cases compared to references.

Conclusions

Increased healthcare use was seen relatively closely to the time of diagnosis for women with OC. This indicates a narrow window of opportunity for a timelier diagnosis. Still, the use of specialised assessment increased at six to eight months before the diagnosis. When women present unspecific symptoms, awareness of potential ovarian malignancies and safety-netting by the general practitioner may be pivotal.

Trial registration

Not relevant.
Added value of the pulmonary vein pulsatility index and its correlation to neonatal umbilical artery pH in fetal growth restrictions: a Vietnamese matched cohort study
Authors: Pham Minh Son , Tran Dinh Vinh , Pham Chi Kong , Truong Thi Linh Giang , Nguyen Vu Quoc Huy
Published: August 2023

Background

In clinical obstetrics, many guidelines recommended the use of Doppler fetal ductus venosus blood flow to monitor and to manage fetal growth restriction (FGR). The ductus venosus and the pulmonary venous flow pattern of fetuses are similar. Umbilical artery pH (UA pH) is essential in identifying adverse pregnancy outcomes, particularly in fetal growth restriction cases. Nevertheless, the literature indicates that the relationship between pulmonary vein pulsatility index (PVPI) and UA pH in FGR cases has not been well investigated. This study aimed to identify the alteration in PVPI in FGR cases and evaluate the correlation between PVPI and UA pH in FGR newborns.

Methods

This matched cohort study of singleton pregnancies from 28+ 0 to 40+ 0 weeks of gestation without congenital abnormalities included 135 cases of FGR (disease group) and 135 cases of normal growth (control group). The PVPI was measured at the proximal segment of the right or left pulmonary vein, approximately 5 mm from the left atrium wall. The umbilical artery pulsatility index (UAPI) was measured on the free umbilical cord. An elective cesarean section or labor induction are both options for ending the pregnancy, depending on the condition of the mother or fetus. Umbilical artery blood samples were collected within 5 min of delivery for UA pH measurement. SPSS version 20 and Medcalc version 20.1 were used for data analysis.

Results

FGR cases had a significantly higher mean fetal PVPI than the control group (1.16 ± 0.26 vs. 0.84 ± 0.16; p < 0.01), and PVPI and UAPI were positively correlated (r = 0.63; p < 0.001). PVPI and UA pH were negatively correlated in FGR patients, with r = -0.68; p < 0.001. The PVPI value on the 95th percentile had a prognostic value of UA pH < 7.20 with a sensitivity of 88.2%, specificity of 66.3%, positive predictive value of 46.9%, and negative predictive value of 94.3%.

Conclusions

There was a statistically significant difference in PVPI values in FGR cases compared to the normal growth group, a positive correlation between PVPI and UAPI, and a negative correlation between PVPI and UA pH. PVPI might have a prognostic meaning in predicting UA pH at birth.
Baseline serum tumor markers predict the survival of patients with advanced non-small cell lung cancer receiving first-line immunotherapy: a multicenter retrospective study
Authors: Huang Jian , Xiao Yi , Zhou Yubin , Deng Huiyin , Yuan Zihao , Dong Longyan , Lan Jun , Li Xiane , Liu Gaijiao , Hu Hao , Huang Shaohong , Yang Xiongwen
Published: August 2023

Background

This study aimed to investigate the association between baseline serum tumor markers (STMs) (carcinoembryonic antigen [CEA], neuron-specific enolase [NSE], cytokeratin-19 fragment [CYFRA21-1], carbohydrate antigen 19–9 [CA19-9], and carbohydrate antigen 125 [CA125]) and the efficacy of first-line immunotherapy in patients with advanced non-small cell lung cancer.

Methods

This multicenter retrospective study evaluated patients who received first-line immunotherapy between July 2017 and July 2022. The endpoints were progression-free survival (PFS) and overall survival (OS), as defined by the Response Evaluation Criteria in Solid Tumors version 1.1. We divided the patients into three groups based on STM levels: Group A ≥ threefold upper limit of normal, threefold upper limit of normal > Group B > upper limit of normal, and Group C ≤ upper limit of normal.

Results

In total, 716 patients were included in this study. In Cox proportional hazards analyses, the STM levels in Group C were independently associated with superior PFS and OS in patients with lung adenocarcinoma (LUAD). Except for CA19-9 level, the STM levels in Group C were independently associated with superior PFS and OS in patients with lung squamous carcinoma (LUSC). Except for CEA and CA19-9 levels, the levels in Group A were independently associated with inferior PFS and OS in patients with LUAD and LUSC.

Conclusions

Serum CEA, NSE, CYFRA21-1, and CA125 levels can predict PFS and OS in patients with LUAD and LUSC, and serum CA19-9 levels can predict PFS and OS in patients with LUAD. The higher the serum NSE, CYFRA21-1, and CA125 levels, the worse the PFS and OS in patients with LUAD and LUSC. In addition, the higher the serum CA19-9 level, the worse the OS in patients with LUAD.
The relationship between screen time before bedtime and behaviors of preschoolers with autism spectrum disorder and the mediating effects of sleep
Authors: Dong Hanyu , Wang Tiantian , Feng Junyan , Xue Yang , Jia Feiyong
Published: August 2023

Background

There are overlapping effects of screen time and sleep on children’s behavior. The purpose of this study was to explore the relationship of screen time with behavior problems in children with autism spectrum disorder (ASD) and the probable mediating effects of sleep, in order to provide evidence for the need for clinical identification and intervention.

Methods

A sample of 358 preschoolers with ASD were included. We investigated the children’s basic characteristics of sex and age, ASD symptoms (ABC, CARS, and ADOS-2), neurodevelopment (GDS-C), sleep habits (CSHQ), and behavior (CBCL). Pearson correlation tests were used to determine the direct correlations among children’s screen time, CBCL, and CSHQ. Linear regression analysis was used to explore whether screen time predicted total score of CBCL. Multi-step linear regression analysis was used to investigate the mediating effect of sleep on the relationship between screen time and total score of CBCL.

Results

Screen time before bedtime was correlated with CBCL and CSHQ, which indicated that screen time before bedtime was correlated with sleep and behavior in children with ASD. Screen time before bedtime was a predictor of CBCL total score (indicating children’s behavior), and CSHQ total score (indicating children’s sleep habits) played a partial mediating role between screen time before bedtime and children’s behavior.

Conclusion

Clinicians should support and educate parents of children with ASD, which should focus on managing screen time, especially screen time before bedtime.
Explaining variance in self-efficacy among adolescents: the association between mastery experiences, social support, and self-efficacy
Authors: Kleppang Annette Løvheim , Steigen Anne Mari , Finbråten Hanne Søberg
Published: August 2023

Background

Self-efficacy has been identified as an important health-promoting factor for both physical and mental health. Previous studies have examined self-efficacy as a moderating factor between negative psychosocial influences and various outcomes, e.g., life satisfaction and stressors. There is, however, limited knowledge about factors that strengthen self-efficacy. The aim of this study is to examine the association between mastery experiences, social support, and self-efficacy among adolescents in secondary schools in Norway.

Methods

This study is based on cross-sectional data from the Ungdata surveys conducted in eastern part of Norway in 2021. The sample comprises 9,221 adolescents aged 13–16. Sequential multivariate linear regression was conducted to explore the association between mastery experiences, social support, and self-efficacy.

Results

The final model (Model 3) explains 25% of the total variance in self-efficacy. The indicators concerning mastery experiences – defined here as the personal experience of success – explain more of the observed variance in self-efficacy than the other independent variables (change in R square = 10.7%). The items ‘felt mastering things’ ‘and ‘felt useful’ make the strongest and most significant contributions to the variance in self-efficacy in the final model (β = 0.25, p < 0.001 and β = 0.16, p < 0.001, respectively), followed by the variables ‘support from friends’ and ‘parental support’ (β = 0.06, p < 0.001 an β = 0.06, p < 0.001).

Conclusions

Mastery experiences are potential sources for creating and strengthening self-efficacy. Awareness of the health-promoting potential in (strengthening) self-efficacy among adolescents is important. Additional research is needed to further explore these associations.
Mental illness stigma as a moderator in the relationship between religiosity and help-seeking attitudes among Muslims from 16 Arab countries
Authors: Fekih-Romdhane Feten , Daher-Nashif Suhad , Stambouli Manel , Alhuwailah Amthal , Helmy Mai , Shuwiekh Hanaa Ahmed Mohamed , Mohamed Lemine Cheikh Mohamed Fadel , Radwan Eqbal , Saquib Juliann , Saquib Nazmus , Fawaz Mirna , Zarrouq Btissame , Naser Abdallah Y. , Obeid Sahar , Saleh Maan , Haider Sanad , Miloud Lahmer , Badrasawi Manal , Hamdan-Mansour Ayman , Barbato Mariapaola , Motwakil Bakhiet Aisha , Khalil Najat Sayem , Adawi Samir , Grein Fatheya , Loch Alexandre Andrade , Cheour Majda , Hallit Souheil
Published: August 2023

Background

Determining the potential barriers responsible for delaying access to care, and elucidating pathways to early intervention should be a priority, especially in Arab countries where mental health resources are limited. To the best of our knowledge, no previous studies have examined the relationship between religiosity, stigma and help-seeking in an Arab Muslim cultural background. Hence, we propose in the present study to test the moderating role of stigma toward mental illness in the relationship between religiosity and help-seeking attitudes among Muslim community people living in different Arab countries.

Method

The current survey is part of a large-scale multinational collaborative project (StIgma of Mental Problems in Arab CounTries [The IMPACT Project]). We carried-out a web-based cross-sectional, and multi-country study between June and November 2021. The final sample comprised 9782 Arab Muslim participants (mean age 29.67 ± 10.80 years, 77.1% females).

Results

Bivariate analyses showed that less stigmatizing attitudes toward mental illness and higher religiosity levels were significantly associated with more favorable help-seeking attitudes. Moderation analyses revealed that the interaction religiosity by mental illness stigma was significantly associated with help-seeking attitudes (Beta = .005; p < .001); at low and moderate levels of stigma, higher religiosity was significantly associated with more favorable help-seeking attitudes.

Conclusion

Our findings preliminarily suggest that mental illness stigma is a modifiable individual factor that seems to strengthen the direct positive effect of religiosity on help-seeking attitudes. This provides potential insights on possible anti-stigma interventions that might help overcome reluctance to counseling in highly religious Arab Muslim communities.
Prevalence of fibromyalgia syndrome in Saudi Arabia: a systematic review and meta-analysis
Authors: Bawazir Yasser
Published: August 2023

Background

The current systematic review and meta-analysis was conducted to estimate the prevalence of fibromyalgia syndrome (FMS) in Saudi Arabia.

Methods

A PRISMA systematic search appraisal and meta-analysis were conducted. A systematic literature search of English publications in PubMed, Embase, PsycINFO, Web of Science, MEDLINE, and Google Scholar, was conducted up to December 2022. Generic, methodological and statistical data was extracted from the eligible studies. Meta-analysis was done using Comprehensive Meta-Analysis Software. The effect size estimates were calculated using the Fail-Safe N test. The funnel plot, Begg’s and Mazumdar’s rank correlation tests were employed to find any potential bias. The strength of the association between two variables is assessed using Kendall’s tau. A fixed-effects model for the meta-analysis.

Results

The literature search yielded a total of 2479 studies. Eight papers were included in the final analysis with sample size ranging 40 to 1686. All studies were cross-sectional except two, which were retrospective. The total number of the participants recruited in the included articles was 4967 (1794 males and 3173 females); with age ranged between 20 and 79 years. There was high heterogeneity among studies articles (Q = 270.187; p-value 0.001); the tau value was 0.179. The pooled event rates and the 95% confidence intervals (CIs) for the prevalence of FMS in Saudi Arabia in a fixed-effects model was 13.4% (95% CI: 0.124–0.144).

Conclusion

Our results clearly demonstrate that FMS is highly prevalent (13.4%) in Saudi Arabia. It also more common among women. The high prevalence of FMS in Saudi Arabia should be seriously considered and planners should take steps to reduce it.
Women’s knowledge and attitudes to the menopause: a comparison of women over 40 who were in the perimenopause, post menopause and those not in the peri or post menopause
Authors: Tariq Bisma , Phillips Samantha , Biswakarma Rina , Talaulikar Vikram , Harper Joyce C
Published: August 2023

Objectives

To evaluate women’s knowledge and attitudes towards the menopause by comparing three groups of women: perimenopause, post menopause and those women not in either the peri or post menopause (other).

Methods

A 35 question online survey was advertised on social media to evaluate women’s attitudes and knowledge of the menopause. Three groups of women were compared: perimenopause, post menopause and those women not in either the peri or post menopause (other).

Results

Most women were completely uninformed or only had some knowledge of the menopause before the age of 40. Most women thought that the menopause should be taught at school, but over 80% had received no menopause education at school themselves. The most popular sources of menopause information were independent websites and friends. Perimenopausal women were significantly more likely than postmenopausal women to use online resources for menopause information. The perimenopausal and postmenopausal groups had more positive attitudes towards the menopause than the other group. 57.5% of postmenopausal women found the menopause difficult or very difficult. Most women were happy about no longer menstruating, although some expressed sadness regarding fertility loss.

Conclusions

Most women had limited knowledge and negative attitudes towards the menopause, leaving them unprepared to cope with the physical and psychological changes associated with this stage of life. Improved menopause education is required to improve quality of life during the menopausal transition and a most positive narrative of life postmenopause.
Whole-genome sequencing reveals adaptations of hairy-footed jerboas (Dipus, Dipodidae) to diverse desert environments
Authors: Peng Xingwen , Cheng Jilong , Li Hong , Feijó Anderson , Xia Lin , Ge Deyan , Wen Zhixin , Yang Qisen
Published: August 2023

Background

Environmental conditions vary among deserts across the world, spanning from hyper-arid to high-elevation deserts. However, prior genomic studies on desert adaptation have focused on desert and non-desert comparisons overlooking the complexity of conditions within deserts. Focusing on the adaptation mechanisms to diverse desert environments will advance our understanding of how species adapt to extreme desert environments. The hairy-footed jerboas are well adapted to diverse desert environments, inhabiting high-altitude arid regions, hyper-arid deserts, and semi-deserts, but the genetic basis of their adaptation to different deserts remains unknown.

Results

Here, we sequenced the whole genome of 83 hairy-footed jerboas from distinct desert zones in China to assess how they responded under contrasting conditions. Population genomics analyses reveal the existence of three species in hairy-footed jerboas distributed in China: Dipus deasyi, Dipus sagitta, and Dipus sowerbyi. Analyses of selection between high-altitude desert (elevation ≥ 3000m) and low-altitude desert (< 500m) populations identified two strongly selected genes, ATR and HIF1AN, associated with intense UV radiation and hypoxia in high-altitude environments. A number of candidate genes involved in energy and water homeostasis were detected in the comparative genomic analyses of hyper-arid desert (average annual precipitation < 70mm) and arid desert (< 200mm) populations versus semi-desert (> 360mm) populations. Hyper-arid desert animals also exhibited stronger adaptive selection in energy homeostasis, suggesting water and resource scarcity may be the main drivers of desert adaptation in hairy-footed jerboas.

Conclusions

Our study challenges the view of deserts as homogeneous environments and shows that distinct genomic adaptations can be found among desert animals depending on their habitats.
Tabby2: a user-friendly web tool for forecasting state-level TB outcomes in the United States
Authors: Swartwood Nicole A. , Testa Christian , Cohen Ted , Marks Suzanne M. , Hill Andrew N. , Beeler Asay Garrett , Cochran Jennifer , Cranston Kevin , Randall Liisa M. , Tibbs Andrew , Horsburgh C. Robert , Salomon Joshua A. , Menzies Nicolas A.
Published: August 2023

Background

In the United States, the tuberculosis (TB) disease burden and associated factors vary substantially across states. While public health agencies must choose how to deploy resources to combat TB and latent tuberculosis infection (LTBI), state-level modeling analyses to inform policy decisions have not been widely available.

Methods

We developed a mathematical model of TB epidemiology linked to a web-based user interface — Tabby2. The model is calibrated to epidemiological and demographic data for the United States, each U.S. state, and the District of Columbia. Users can simulate pre-defined scenarios describing approaches to TB prevention and treatment or create their own intervention scenarios. Location-specific results for epidemiological outcomes, service utilization, costs, and cost-effectiveness are reported as downloadable tables and customizable visualizations. To demonstrate the tool’s functionality, we projected trends in TB outcomes without additional intervention for all 50 states and the District of Columbia. We further undertook a case study of expanded treatment of LTBI among non-U.S.–born individuals in Massachusetts, covering 10% of the target population annually over 2025-2029.

Results

Between 2022 and 2050, TB incidence rates were projected to decline in all states and the District of Columbia. Incidence projections for the year 2050 ranged from 0.03 to 3.8 cases (median 0.95) per 100,000 persons. By 2050, we project that majority (> 50%) of TB will be diagnosed among non-U.S.–born persons in 46 states and the District of Columbia; per state percentages range from 17.4% to 96.7% (median 83.0%). In Massachusetts, expanded testing and treatment for LTBI in this population was projected to reduce cumulative TB cases between 2025 and 2050 by 6.3% and TB-related deaths by 8.4%, relative to base case projections. This intervention had an incremental cost-effectiveness ratio of $180,951 (2020 USD) per quality-adjusted life year gained from the societal perspective.

Conclusions

Tabby2 allows users to estimate the costs, impact, and cost-effectiveness of different TB prevention approaches for multiple geographic areas in the United States. Expanded testing and treatment for LTBI could accelerate declines in TB incidence in the United States, as demonstrated in the Massachusetts case study.
Telehealth in antenatal care: recent insights and advances
Authors: Atkinson Jessica , Hastie Roxanne , Walker Susan , Lindquist Anthea , Tong Stephen
Published: August 2023

Background

For decades, antenatal care in high-resource settings has involved 12–14 face-to-face visits across pregnancy. The COVID-19 pandemic forced many care providers to rapidly embrace telehealth to reduce face-to-face visits. Here we review recent advances in telehealth used to provide antenatal care.

Main body

We conducted a narrative review examining the impact of telehealth on obstetric care. Two broad types of telehealth are used in antenatal care. The first is real-time telehealth, where consultations are done virtually instead of face-to-face. The second is remote monitoring, where in-clinic physical examinations are replaced with at-home alternatives. These can include blood pressure monitoring, fetal heart rate monitoring, and emerging technologies such as tele-ultrasound. Large cohort studies conducted during the pandemic era have shown that telehealth appears not to have increased adverse clinical outcomes for mothers or babies. However, further studies may be required to confidently conclude rare outcomes are unchanged, such as maternal mortality, serious morbidity, or stillbirth. Health economic studies suggest telehealth has the potential to reduce the financial cost of care provision. Telehealth in antenatal care seems to be acceptable to both pregnant women and healthcare providers.

Conclusion

Adoption of telehealth technologies may improve the antenatal care experience for women and reduce healthcare expenditure without adversely impacting health outcomes for the mother or baby. More studies are warranted to confirm telehealth does not alter the risk of rare outcomes such as maternal or neonatal mortality.
Glycolysis-related biomarker TCIRG1 participates in regulation of renal cell carcinoma progression and tumor immune microenvironment by affecting aerobic glycolysis and AKT/mTOR signaling pathway
Authors: Di Sichen , Gong Min , Lv Jianmin , Yang Qiwei , Sun Ye , Tian Yijun , Qian Cheng , Chen Wenjin , Zhou Wang , Dong Keqin , Shi Xiaokai , Wang Yuning , Wang Hongru , Chu Jian , Gan Sishun , Pan Xiuwu , Cui Xingang
Published: August 2023

Background

Renal cell carcinoma (RCC) is a hypermetabolic disease. Abnormal up-regulation of glycolytic signaling promotes tumor growth, and glycolytic metabolism is closely related to immunotherapy of renal cancer. The aim of the present study was to determine whether and how the glycolysis-related biomarker TCIRG1 affects aerobic glycolysis, the tumor microenvironment (TME) and malignant progression of clear cell renal cell carcinoma (ccRCC).

Methods

Based on The Cancer Genome Atlas (TCGA, n = 533) and the glycolysis-related gene set from MSigDB, we identified the glycolysis-related gene TCIRG1 by bioinformatics analysis, analyzed its immunological properties in ccRCC and observed how it affected the biological function and glycolytic metabolism using online databases such as TIMER 2.0, UALCAN, LinkedOmics and in vitro experiments.

Results

It was found that the expression of TCIRG1, was significantly increased in ccRCC tissue, and that high TCIRG1 expression was associated with poor overall survival (OS) and short progression-free interval (PFI). In addition, TCIRG1 expression was highly correlated with the infiltration immune cells, especially CD4+T cell Th1, CD8+T cell, NK cell, and M1 macrophage, and positively correlated with PDCD1, CTLA4 and other immunoinhibitors, CCL5, CXCR3 and other chemokines and chemokine receptors. More importantly, TCIRG1 may regulate aerobic glycolysis in ccRCC via the AKT/mTOR signaling pathway, thereby affecting the malignant progression of ccRCC cell lines.

Conclusions

Our results demonstrate that the glycolysis-related biomarker TCIRG1 is a tumor-promoting factor by affecting aerobic glycolysis and tumor immune microenvironment in ccRCC, and this finding may provide a new idea for the treatment of ccRCC by combination of metabolic intervention and immunotherapy.
Patient-centeredness—a cultural targeted survey among junior medical managers
Authors: Tal Orna , Barnea Royi , Tur-Sinai Aviad
Published: August 2023

Background

Patient-centeredness is a core element in healthcare. However, there is a gap between the understanding of this term by healthcare professionals, and patients’ capability, self-efficacy, and willingness to take part in medical decisions. We aim to expose standpoints toward “patient centeredness” among junior medical managers (JMM), as they bridge between policy strategies and patients. We try to reveal cultural differences by comparing the views of the majority and the minority subpopulations of Israel (Arabic and Hebrew speakers).

Methods

A cross-sectional survey among JMM studying for an advanced degree in health-system management at three academic training colleges in Israel was conducted in February–March 2022. The respondents completed a structured questionnaire comprising four sections: a) perceptions of trust, accountability, insurance coverage, and economic status; b) perceptions regarding decision-making mechanisms; c) preferences toward achieving equity, and d) demographic details.

Results

A total of 192 respondents were included in the study—50% Hebrew speakers and 50% Arabic speakers. No differences were found between Arabic and Hebrew speakers regarding perception of trust, accountability, insurance coverage, and economic status. JMM from both subpopulations believed that patients’ gender and age do not influence physicians’ attitudes but Arabic-speaking respondents perceived that healthcare professionals prefer educated patients or those with supportive families. All respondents believed that patients would like to be more involved in medical decisions; yet Arabic-speakers perceived patients as tending to rely on physicians’ recommendations while Hebrew speakers believed that patients wish to lead the medical decision by themselves.

Conclusions

Patient-centeredness strategy needs to be implemented bottom-up as well as top-down, in a transparent nationwide manner. JMM are key actors in carrying out this strategy because they realize policy guidelines in the context of social disparities, enabling them to achieve a friendly personalized dialogue with their patients. We believe that empowering these JMM may create a ripple effect, yielding a bottom-up perception of equity and initiating change.
Beyond the anti-PD-1/PD-L1 era: promising role of the BTLA/HVEM axis as a future target for cancer immunotherapy
Authors: Sordo-Bahamonde Christian , Lorenzo-Herrero Seila , Granda-Díaz Rocío , Martínez-Pérez Alejandra , Aguilar-García Candelaria , Rodrigo Juan P. , García-Pedrero Juana M. , Gonzalez Segundo
Published: August 2023

Recent introduction of monoclonal antibodies targeting immune checkpoints to harness antitumor immunity has revolutionized the cancer treatment landscape. The therapeutic success of immune checkpoint blockade (ICB)-based therapies mainly relies on PD-1/PD-L1 and CTLA-4 blockade. However, the limited overall responses and lack of reliable predictive biomarkers of patient´s response are major pitfalls limiting immunotherapy success. Hence, this reflects the compelling need of unveiling novel targets for immunotherapy that allow to expand the spectrum of ICB-based strategies to achieve optimal therapeutic efficacy and benefit for cancer patients. This review thoroughly dissects current molecular and functional knowledge of BTLA/HVEM axis and the future perspectives to become a target for cancer immunotherapy. BTLA/HVEM dysregulation is commonly found and linked to poor prognosis in solid and hematological malignancies. Moreover, circulating BTLA has been revealed as a blood-based predictive biomarker of immunotherapy response in various cancers. On this basis, BTLA/HVEM axis emerges as a novel promising target for cancer immunotherapy. This prompted rapid development and clinical testing of the anti-BTLA blocking antibody Tifcemalimab/icatolimab as the first BTLA-targeted therapy in various ongoing phase I clinical trials with encouraging results on preliminary efficacy and safety profile as monotherapy and combined with other anti-PD-1/PD-L1 therapies. Nevertheless, it is anticipated that the intricate signaling network constituted by BTLA/HVEM/CD160/LIGHT involved in immune response regulation, tumor development and tumor microenvironment could limit therapeutic success. Therefore, in-depth functional characterization in different cancer settings is highly recommended for adequate design and implementation of BTLA-targeted therapies to guarantee the best clinical outcomes to benefit cancer patients.
Short-term intensive fasting enhances the immune function of red blood cells in humans
Authors: Fang Yixuan , Qian Jiawei , Xu Li , Wei Wen , Bu Wenwen , Zhang Suping , Lv Yaqi , Li Lei , Zhao Chen , Gao Xueqin , Gu Yue , Wang Li , Chen Zixing , Wang Xiao , Zhang Ruizhi , Xu Youjia , Yang Yanjun , Lu Jie , Yan Zhanjun , Wang Mingyuan , Tang Longhai , Yuan Na , Wang Jianrong
Published: August 2023

Background

Fasting is known to influence the immune functions of leukocytes primarily by regulating their mobilization and redistribution between the bone marrow and the peripheral tissues or circulation, in particular via relocalization of leukocytes back in the bone marrow. However, how the immune system responds to the increased risk of invasion by infectious pathogens with fewer leukocytes in the peripheral blood during fasting intervention remains an open question.

Results

We used proteomic, biochemical and flow cytometric tools to evaluate the impact of short-term intensive fasting (STIF), known as beego, on red blood cells by profiling the cells from the STIF subjects before and after 6 days of fasting and 6 days of gradual refeeding. We found that STIF, by triggering the activation of the complement system via the complement receptor on the membrane of red blood cells, boosts fairly sustainable function of red blood cells in immune responses in close relation to various pathogens, including viruses, bacteria and parasites, particularly with the pronounced capacity to defend against SARS-CoV-2, without compromising their oxygen delivery capacity and viability.

Conclusion

STIF fosters the immune function of red blood cells and therefore, it may be considered as a nonmedical intervention option for the stronger capacity of red blood cells to combat infectious diseases.
Geniposide suppressed OX-LDL-induced osteoblast apoptosis by regulating the NRF2/NF-κB signaling pathway
Authors: Xiao Yaosheng , Zhang Shanshan , Ye Yongjun , Chen Jincai , Xu Youjia
Published: August 2023

Background

Osteoporosis (OP), due to microarchitectural alterations, is associated with decreased bone mass, declined strength, and increased fracture risk. Increased osteoblast apoptosis contributes to the progression of OP. Natural compounds from herbs provide a rich resource for drug screening. Our previous investigation showed that geniposide (GEN), an effective compound from Eucommia ulmoides, could protect against the pathological development of OP induced by cholesterol accumulation.

Methods

The rat OP models were duplicated. Dual-energy X-ray absorptiometry, hematoxylin and eosin staining, and immunohistochemistry were used to evaluate bone changes. TUNEL/DAPI staining assays were used for cell apoptosis detection. Protein expression was determined by western blotting assays.

Results

A high-fat diet promoted OP development in vivo, and OX-LDL stimulated osteoblast apoptosis in vitro. GEN exhibited protective activities against OX-LDL-induced osteoblast apoptosis by increasing the NRF2 pathway and decreasing the NF-κB pathway. PDTC, an NF-κB inhibitor, could further promote the biological functions of GEN. In contrast, ML385, an NRF2 inhibitor, might eliminate GEN’s protection.

Conclusion

GEN suppressed OX-LDL-induced osteoblast apoptosis by regulating the NRF2/NF-κB signaling pathway.
MUC16 stimulates neutrophils to an inflammatory and immunosuppressive phenotype in ovarian cancer
Authors: Wu Yuliang , Liu Qi , Xie Yan , Zhu Jihui , Zhang Sai , Ge Yao , Guo Jing , Luo Ning , Huang Wei , Xu Runping , Liu Shupeng , Cheng Zhongping
Published: August 2023

Background

MUC16 (CA125) is a commonly used tumor marker for ovarian cancer screening and reported to be an immunosuppressive factor by acting on the sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) on the surface of natural killer cells (NK cells), B cells, and monocytes. However, the role of MUC16 on neutrophils in the tumor microenvironment remains to be further explored.

Methods

The correlation between the proportion and count of peripheral blood cells, serum inflammatory-related factors and serum MUC16 (CA125) level in patients was constructed based on clinical samples. RNAseq data was obtained from TCGA and sequencing of ovarian cancer tissues, followed by TIMER immune cell infiltration and correlation analysis. Ovarian cancer organoid was constructed to stimulate neutrophils with immunophenotype identification by qPCR and flow cytometry. MUC16 protein stimulation to neutrophils validated the role of MUC16 under the analysis of RNA sequencing and inhibition of NK cytotoxicity in vitro.

Results

The serum MUC16 level was positively correlated with the proportion and count of peripheral blood neutrophils, neutrophil-to-lymphocyte ratio (NLR) and inflammatory factors IL-6, IL-8, IL-10 and IL-2R. Siglec-9, the receptor of MUC16, was expressed on neutrophils and was positively correlated to neutrophil infiltration in ovarian cancer. After the stimulation of ovarian cancer organoids and MUC16 respectively, the proportions of CD11b+, CD66b+, and ICAM-1+ neutrophils were significantly increased, while the proportion of CXCR4+ neutrophils was slightly decreased, with increasing of of inflammatory factors MMP9, IL-8, OSM, IL-1β, TNF-α, CXCL3, and ROS. RNA-sequencing analysis revealed that inflammatory response, TNFA signaling pathway, and IL6-related pathway were upregulated in MUC16-stimulated neutrophils, accompanied by high expression of immunosuppression-related factors HHLA2, IL-6, TNFRSF9, ADORA2A, CD274 (PD-L1), and IDO1. NK cytotoxicity was decreased when treated by supernanant of MUC16-stimulated neutrophils in vitro.

Conclusion

MUC16 acted on neutrophils by Siglec-9 leading to an inflammatory and immunosuppressive phenotype in ovarian cancer.