bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetically proxied therapeutic prolyl-hydroxylase inhibition and cardiovascular risk
Authors: Harlow Charli E , Patel Vickas V , Waterworth Dawn M , Wood Andrew R , Beaumont Robin N , Ruth Katherine S , Tyrrell Jessica , Oguro-Ando Asami , Chu Audrey Y , Frayling Timothy M
Published: September 2022

Prolyl hydroxylase (PHD) inhibitors are in clinical development for anaemia in chronic kidney disease. Epidemiological studies have reported conflicting results regarding safety of long-term therapeutic haemoglobin (Hgb) rises through PHD inhibition on risk of cardiovascular disease. Genetic variation in genes encoding PHDs can be used as partial proxies to investigate the potential effects of long-term Hgb rises. We used Mendelian randomization to investigate the effect of long-term Hgb level rises through genetically proxied PHD inhibition on coronary artery disease (CAD: 60 801 cases; 123 504 controls), myocardial infarction (MI: 42 561 cases; 123 504 controls) or stroke (40 585 cases; 406 111 controls). To further characterize long-term effects of Hgb level rises, we performed a phenome-wide association study (PheWAS) in up to 451 099 UK Biobank individuals. Genetically proxied therapeutic PHD inhibition, equivalent to a 1.00 g/dl increase in Hgb levels, was not associated (at P < 0.05) with increased odds of CAD; odd ratio (OR) [95% confidence intervals (CI)] = 1.06 (0.84, 1.35), MI [OR (95% CI) = 1.02 (0.79, 1.33)] or stroke [OR (95% CI) = 0.91 (0.66, 1.24)]. PheWAS revealed associations with blood related phenotypes consistent with EGLN’s role, relevant kidney- and liver-related biomarkers like estimated glomerular filtration rate and microalbuminuria, and non-alcoholic fatty liver disease (Bonferroni-adjusted P < 5.42E-05) but these were not clinically meaningful. These findings suggest that long-term alterations in Hgb through PHD inhibition are unlikely to substantially increase cardiovascular disease risk; using large disease genome-wide association study data, we could exclude ORs of 1.35 for cardiovascular risk with a 1.00 g/dl increase in Hgb.
Combinatorial treatment with exercise and AICAR potentiates the rescue of myotonic dystrophy type 1 mouse muscles in a sex-specific manner
Authors: Misquitta Naomi S , Ravel-Chapuis Aymeric , Jasmin Bernard J
Published: September 2022

Targeting AMP-activated protein kinase (AMPK) is emerging as a promising strategy for treating myotonic dystrophy type 1 (DM1), the most prevalent form of adult-onset muscular dystrophy. We previously demonstrated that 5-aminomidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) and exercise, two potent AMPK activators, improve disease features in DM1 mouse skeletal muscles. Here, we employed a combinatorial approach with these AMPK activators and examined their joint impact on disease severity in male and female DM1 mice. Our data reveal that swimming exercise additively enhances the effect of AICAR in mitigating the nuclear accumulation of toxic CUGexp RNA foci. In addition, our findings show a trend towards an enhanced reversal of MBNL1 sequestration and correction in pathogenic alternative splicing events. Our results further demonstrate that the combinatorial impact of exercise and AICAR promotes muscle fiber hypertrophy in DM1 skeletal muscle. Importantly, these improvements occur in a sex-specific manner with greater benefits observed in female DM1 mice. Our findings demonstrate that combining AMPK-activating interventions may prove optimal for rescuing the DM1 muscle phenotype and uncover important sex differences in the response to AMPK-based therapeutic strategies in DM1 mice.
A non-coding variant in 5’ untranslated region drove up-regulation of pseudo-kinase EPHA10 and caused non-syndromic hearing loss in humans
Authors: Huang Sida , Ma Lu , Liu Xuezhong , He Chufeng , Li Jiada , Hu Zhengmao , Jiang Lu , Liu Yalan , Liu Xianlin , Feng Yong , Cai Xinzhang
Published: September 2022

Hereditary hearing loss has a genetic and phenotypic heterogeneity. However, it is still difficult to explain this heterogeneity perfectly with known deafness genes. Here, we report a novel causative gene EPHA10 as well as its non-coding variant in 5′ untranslated region identified in a family with post-lingual autosomal dominant non-syndromic hearing loss from southern China. One affected member of this family had an ideal hearing restoration after cochlear implantation. We speculated that there were probable deafness-causing abnormalities in the cochlea according to clinical imaging and auditory evaluations. A heterozygous variant c.-81_-73delinsAGC was found co-segregating with hearing loss. Epha10 was expressed in mouse cochlea at both transcription and translation levels. The variant caused upregulation of EPHA10 which may result from promoter activity enhancement after sequence change. Overexpression of Eph (the homolog of human EPHA10) exerted effects on the structure and function of chordotonal organ in fly model. In summary, our study linked pseudo-kinase EPHA10 to hearing loss in humans for the first time.
Validating the Simplified Endoscopic Mucosal Assessment for Crohn’s Disease: A Novel Method for Assessing Disease Activity
Authors: Adler Jeremy , Colletti Richard B , Noonan Lenore , Berzin Tyler M , Cheifetz Adam S , Conklin Laurie S , Hoops Timothy C , Huang Christopher S , Lewis Blair , Mishkin Daniel S , Hung Lo Kim , Xiao Yongling , Volger Sheri
Published: September 2022

Background

To demonstrate treatment efficacy in Crohn’s disease (CD), regulatory authorities require that trials include an endoscopic remission/response end point; however, standardized endoscopic assessment of disease activity, such as the Simple Endoscopic Score for Crohn’s Disease (SES-CD), is not typically recorded by clinicians in practice or outside of clinical trials. The novel Simplified Endoscopic Mucosal Assessment for Crohn’s Disease (SEMA-CD) was developed to be easy to use in routine clinical practice and as a trial end point. We conducted a study to assess and validate the reliability and feasibility of SEMA-CD as a measure of endoscopic disease activity.

Methods

Pre- and post-treatment ileocolonoscopy videos of pediatric (n = 36) and adult (n = 74) CD patients from 2 ustekinumab clinical trials were each scored with SEMA-CD by 2 to 3 professional central readers, blinded to clinical history and other video scorings; the correlation between SEMA-CD and SES-CD previously completed during the trials was assessed. Sensitivity to change, inter- and intrarater reliability, and comparative ease of scoring were also assessed.

Results

The SEMA-CD strongly correlated with SES-CD (Spearman ρ = 0.89; 95% confidence interval, 0.86-0.92). Pre- to post-treatment changes in SEMA-CD vs in SES-CD were strongly correlated, and the correlation remained strong between the scores when compared by study population (pediatric, adult), disease severity, and video quality. Intra- and inter-rater reliability were good, and SEMA-CD was rated easier than SES-CD to score 63.0% of the time, although slightly more difficult than SES-CD to score <1.0% of the time.

Conclusions

The SEMA-CD is reliable, reproducible, sensitive to change, and easy to use in both pediatric and adult patients with CD.
Peripartum Infections Among Women With Inflammatory Bowel Disease
Authors: Narkis Bar , Hadar Eran , Barbash-Hazan Shiri , Houri Ohad , Shay Vardit , Ollech Jacob E , Yanai Henit , Dotan Iris , Avni-Biron Irit
Published: September 2022

Background

Pregnant patients with inflammatory bowel diseases (IBDs) are frequently treated with immunomodulatory agents and may be at increased risk of adverse outcomes, including peripartum infections. We sought to examine the risk for peripartum infections in patients with IBD compared with control subjects and identify potential risk factors associated with peripartum infections in these patients.

Methods

This retrospective cohort study compared peripartum infection rates and associated risk factors between pregnant women with and without IBD. The study population included women attending a dedicated joint maternal-fetal medicine and gastroenterology clinic for pregnant women with IBD between 2012 and 2019 at the Rabin Medical Center in Israel, a major referral center for patients with IBD. For each patient, 5 women without IBD were matched according to the newborn’s birth date (±2 years), age, parity, and body mass index. Peripartum infection was defined as any 1 of the following: chorioamnionitis, maternal fever (>38°C) detected during labor or postpartum hospitalization, and positive culture taken during the hospitalization.

Results

Overall, 195 pregnant women with IBD (72 [37%] with ulcerative colitis, 123 [63%] with Crohn’s disease) were matched with 888 control subjects. The mean disease duration was 8.4 ± 7.02 years. IBD therapy, used by 81%, included most frequently 5-aminosalicylic acid (44%) and tumor necrosis factor inhibitors (27%). Peripartum infections were observed in 15 (7.7%) patients and 49 (5.5%) control subjects (P = 1.00). No medication significantly increased the likelihood of peripartum infection. Cesarean delivery was more likely among women with IBD but was not associated with an increased risk of peripartum infection.

Conclusions

Peripartum infections were comparable in patients with IBD and control subjects. These reassuring data augment existing knowledge of obstetrical outcomes in IBD patients and contribute to the discussion between caregivers and patients.
Irrigation-Induced Environmental Changes Sustain Malaria Transmission and Compromise Intervention Effectiveness
Authors: Zhou Guofa , Hemming-Schroeder Elizabeth , Jeang Brook , Wang Xiaoming , Zhong Daibin , Lee Ming-Chieh , Li Yiji , Bradley Lauren , Gobran Sabrina R , David Randy E , Ondeto Benyl M , Orondo Pauline , Atieli Harrysone , Githure John I , Githeko Andrew K , Kazura James , Yan Guiyun
Published: September 2022

Background

Irrigated agriculture enhances food security, but it potentially promotes mosquito-borne disease transmission and affects vector intervention effectiveness. This study was conducted in the irrigated and nonirrigated areas of rural Homa Bay and Kisumu Counties, Kenya.

Methods

We performed cross-sectional and longitudinal surveys to determine Plasmodium infection prevalence, clinical malaria incidence, molecular force of infection (molFOI), and multiplicity of infection. We examined the impact of irrigation on the effectiveness of the new interventions.

Results

We found that irrigation was associated with >2-fold higher Plasmodium infection prevalence and 3-fold higher clinical malaria incidence compared to the nonirrigated area. Residents in the irrigated area experienced persistent, low-density parasite infections and higher molFOI. Addition of indoor residual spraying was effective in reducing malaria burden, but the reduction was more pronounced in the nonirrigated area than in the irrigated area.

Conclusions

Our findings collectively suggest that irrigation may sustain and enhance Plasmodium transmission and affects intervention effectiveness.
Prevalence of and factors associated with early initiation of breastfeeding in Bangladesh: a multilevel modelling
Authors: Kundu Satyajit , Azene Abebaw Gedef , Kundu Subarna , Banna Md Hasan Al , Mahbub Tahira , Alshahrani Najim Z , Rahman Md Ashfikur
Published: September 2022

Background

Early initiation breastfeeding (EIBF) is a sign of good health for both the mother and the newborn baby. The objective of this study was to estimate the prevalence of EIBF among mothers in Bangladesh and to identify its associated factors.

Methods

The study used the most recent Bangladesh Demographic and Health Survey 2017–2018 data. A total of 4776 (weighted) respondents were included in the final analysis. The association between the outcome and the independent variables was determined using multilevel (mixed effects) logistic regression analysis.

Results

The overall weighted prevalence of EIBF among Bangladeshi mothers was 61.19% (confidence interval [CI] 59.80 to 62.56). The study shows that non-poor wealth status (adjusted odds ratio [AOR] 0.81 [95% CI 0.68 to 0.95]), institutional delivery (AOR 0.77 [95% CI 0.61 to 0.96]) and caesarean delivery (AOR 0.31 [95% CI 0.26 to 0.38]) were associated with the lower odds of EIBF. Mother's secondary education (AOR 1.34 [95% CI 1.01 to 1.83]), at least four antenatal care visits (AOR 1.36 [95% CI 1.04 to 1.53]), normal birthweight (AOR 1.42 [95% CI 1.09 to 1.85]) and placed on mother's chest and bare skin after birth (AOR 1.33 [95% CI 1.11 to 1.60]) were associated with higher odds of EIBF.

Conclusion

In order to enhance EIBF in Bangladesh, health professionals should emphasise skin-to-skin contact after delivery.
Disruption of the intestinal barrier exacerbates experimental autoimmune pancreatitis by promoting the translocation ofStaphylococcus sciuriinto the pancreas
Authors: Yoshikawa Tomoe , Minaga Kosuke , Hara Akane , Sekai Ikue , Kurimoto Masayuki , Masuta Yasuhiro , Otsuka Yasuo , Takada Ryutaro , Kamata Ken , Park Ah-Mee , Takamura Shiki , Kudo Masatoshi , Watanabe Tomohiro
Published: September 2022

Autoimmune pancreatitis (AIP) and IgG4-related disease (IgG4-RD) are new disease entities characterized by enhanced IgG4 antibody responses and involvement of multiple organs, including the pancreas and salivary glands. Although the immunopathogenesis of AIP and IgG4-RD is poorly understood, we previously reported that intestinal dysbiosis mediates experimental AIP through the activation of IFN-α- and IL-33-producing plasmacytoid dendritic cells (pDCs). Because intestinal dysbiosis is linked to intestinal barrier dysfunction, we explored whether the latter affects the development of AIP and autoimmune sialadenitis in MRL/MpJ mice treated with repeated injections of polyinosinic–polycytidylic acid [poly (I:C)]. Epithelial barrier disruption was induced by the administration of dextran sodium sulfate (DSS) in the drinking water. Mice co-treated with poly (I:C) and DSS, but not those treated with either agent alone, developed severe AIP, but not autoimmune sialadenitis, which was accompanied by the increased accumulation of IFN-α- and IL-33-producing pDCs. Sequencing of 16S ribosomal RNA revealed that Staphylococcus sciuri translocation from the gut to the pancreas was preferentially observed in mice with severe AIP co-treated with DSS and poly (I:C). The degree of experimental AIP, but not of autoimmune sialadenitis, was greater in germ-free mice mono-colonized with S. sciuri and treated with poly (I:C) than in germ-free mice treated with poly (I:C) alone, which was accompanied by the increased accumulation of IFN-α- and IL-33-producing pDCs. Taken together, these data suggest that intestinal barrier dysfunction exacerbates AIP through the activation of pDCs and translocation of S. sciuri into the pancreas.
SARS-CoV-2 ORF8 is a viral cytokine regulating immune responses
Authors: Kohyama Masako , Suzuki Tatsuya , Nakai Wataru , Ono Chikako , Matsuoka Sumiko , Iwatani Koichi , Liu Yafei , Sakai Yusuke , Nakagawa Atsushi , Tomii Keisuke , Ohmura Koichiro , Okada Masato , Matsuura Yoshiharu , Ohshima Shiro , Maeda Yusuke , Okamoto Toru , Arase Hisashi
Published: September 2022

Many patients with severe COVID-19 suffer from pneumonia and the elucidation of the mechanisms underlying the development of this severe condition is important. The in vivo function of the ORF8 protein secreted by SARS-CoV-2 is not well understood. Here, we analyzed the function of ORF8 protein by generating ORF8-knockout SARS-CoV-2 and found that the lung inflammation observed in wild-type SARS-CoV-2-infected hamsters was decreased in ORF8-knockout SARS-CoV-2-infected hamsters. Administration of recombinant ORF8 protein to hamsters also induced lymphocyte infiltration into the lungs. Similar pro-inflammatory cytokine production was observed in primary human monocytes treated with recombinant ORF8 protein. Furthermore, we demonstrated that the serum ORF8 protein levels are well-correlated with clinical markers of inflammation. These results demonstrated that the ORF8 protein is a SARS-CoV-2 viral cytokine involved in the immune dysregulation observed in COVID-19 patients, and that the ORF8 protein could be a novel therapeutic target in severe COVID-19 patients.
The attitudes of hospital directors towards normalising accreditation standards: A qualitative descriptive study for Saudi Arabia
Authors: Hussein Mohammed , Pavlova Milena , Groot Wim
Published: September 2022

Background

Accreditation is an important performance management tool. The engagement of stakeholders in pursuing accreditation plays a critical role in integrating standards into routine practice.

Objective

This study explores the attitude of hospital directors towards accreditation and investigates the mechanisms of normalising standards in Saudi Arabian hospitals.

Methods

Fifteen hospital directors across Saudi Arabia participated in semi-structured qualitative interviews. The interviews were conducted virtually, audiotaped, transcribed verbatim, and then analysed thematically using the NVivo-12 software package. The normalisation process theory (i.e. coherence, participation, actions and monitoring) was adopted to frame the study and describe the findings on normalising accreditation standards heuristically.

Results

Overall, the hospital directors perceived accreditation favourably, particularly by those with more experience or previous exposure to accreditation. This attitude was a factor in normalising standards into daily operations. The clarity of standards, availability of full-time quality professionals and alignment of accreditation standards with hospital strategies assisted hospital directors in making sense of accreditation (coherence) and moving towards engaging hospital teams in the process (cognitive participation). This motivation-driven engagement catalysed the initiation of purposeful operational activities to integrate standards in operations (collective actions). The integration included distributing standard sets to relevant owners, conducting gap analysis, constructing a corrective plan and prioritising tasks within timeframes. Despite the financial and structural constraints experienced, the integration resulted in enhanced organisational safety culture, team spirit, communication, public trust, reporting of safety concerns and standardising of procedures. Following the integration, the objective appraisal of accreditation benefits (reflexive monitoring) was critical in addressing what went wrong, what worked well, and subsequently in sustaining performance gains.

Conclusion

The effectiveness of integrating accreditation standards heavily relies on making sense of accreditation and understanding the mechanisms through which standards are routinised into operations. This study, using normalisation process theory constructs, indicates that standards integration phases are sequential, interlinked and influenced by culture, teamwork and leadership engagement. The findings helped in clarifying the accreditation operating process which may provide advantages to policymakers and stakeholders in making informed decisions on the implementation of accreditation.
Picture a data scientist: a call to action for increasing diversity, equity, and inclusion in the age of AI
Authors: de Hond Anne A H , van Buchem Marieke M , Hernandez-Boussard Tina
Published: September 2022

The lack of diversity, equity, and inclusion continues to hamper the artificial intelligence (AI) field and is especially problematic for healthcare applications. In this article, we expand on the need for diversity, equity, and inclusion, specifically focusing on the composition of AI teams. We call to action leaders at all levels to make team inclusivity and diversity the centerpieces of AI development, not the afterthought. These recommendations take into consideration mitigation at several levels, including outreach programs at the local level, diversity statements at the academic level, and regulatory steps at the federal level.
Insulin-like growth factor-1 is involved in the deteriorated performance of aged laying hens
Authors: Xin Qian , Uyanga Victoria Anthony , Jiao Hongchao , Zhao Jingpeng , Wang Xiaojuan , Li Haifang , Zhou Yunlei , Lin Hai
Published: September 2022

The underlying mechanism behind the deteriorated laying performance of aged laying hens remains unclear. In the present study, the laying performance and gene expression along the hypothalamus-pituitary-gonad axis were determined. A total of 300 healthy 90-wk-old ISA hens with similar body weights were classified into three groups according to their laying rate between 90 and 94 wk of age. The experimental groups were the low laying rate (<60%, LLR), high laying rate (>85%, HLR), and intermediate laying rate (60% < laying rate < 85%, MLR) hens. At the end of 94 wk of age, eight hens were randomly selected from each group for tissue collection. The gene expression of hormones and their receptors were determined in the hypothalamus, pituitary, and follicles. The results showed that the serum 17-β-estradiol had no significant difference among the three groups. However, the level of insulin-like growth factor 1 (IGF1) in LLR hens was significantly decreased in the serum, small white follicles (SWF), and dominant follicles (DF, P < 0.05). Within the hypothalamus and small yellow follicles (SYF), the mRNA expression level of estrogen receptor was higher in the MLR group (P < 0.05). Compared with HLR hens, the steroid hormone-synthesis key gene, CYP19A1 was significantly decreased in the SWF of MLR-hens and DF of MLR- and LLR-hens (P < 0.05). The mRNA expression level of IGF1 receptor was higher in the hypothalamus, pituitary, SWF, large white follicles (LWF), SYF, and DF of LLR hens, compared to the HLR hens (P < 0.05). These results suggest that decreased IGF1 in serum and follicles was associated with the decreased egg production of aged laying hens. The present study provides novel insights into the endocrine changes in aged hens having different egg production.
Burn Wound Bed Management
Authors: Wong She Richard B , Gibran Nicole S
Published: September 2022

Critical to the success of modern burn care is the management of the burn wound. Timely and complete removal of nonviable tissue is complicated by the irreplaceable nature of the tissue lost either through the burn injury or as “collateral damage” as part of the treatment. Challenges in distinguishing between viable and nonviable tissue and “replacing the irreplaceable” are discussed alongside potential disruptive technologies which could fundamentally change how burn care is delivered. Advances in burn wound bed management forms the foundation on which the goal of zero preventable death and disability after burn injury can be achieved.
TransNav: spatial sequential transformer network for visual navigation
Authors: Zhou Kang , Zhang Huyin , Li Fei
Published: September 2022

Visual navigation task is to steer an embodied agent finding the given target based on observation. The effective transformer from observation of the agent to visual representation determines the navigation actions and promotes more informed navigation policy. In this work, we propose a spatial sequential transformer network (SSTNet) for learning informative visual representation in deep reinforcement learning. SSTNet is composed by spatial attention probability fused model (SAF) and sequential transformer network (STNet). SAF enforces cross-modal state into visual clues in reinforcement learning. It encodes semantic information about observed objects, as well as spatial information about their location, which jointly exploiting image inter-relations. STNet generates (imagines) the next observations and makes action inference of the aspects most relevant to the target. It decodes the image intra-relations. This way, the agent learns to understand the causality between navigation actions and dynamic changes in observations. SSTNet is conditioned on an auto-regressive model on the desired reward, past states, actions, and knowledge graph. The whole navigation framework considers the local and global visual information, as well as time sequential information. Thus, it allows the agent to navigate towards the sought-after object effectively. We evaluate our model on the AI2THOR framework show that our method attains at least $10\%$ improvement of average success rate over most state-of-the-art models. Code and datasets can be found in https://github.com/zhoukang123/SDTNet_2022.
The phylogeny of California, and how it informs setting multispecies conservation priorities
Authors: Toffelmier Erin , Beninde Joscha , Shaffer H Bradley
Published: September 2022

Incorporating measures of taxonomic diversity into research and management plans has long been a tenet of conservation science. Increasingly, active conservation programs are turning toward multispecies landscape and regional conservation actions, and away from single species approaches. This is both a reflection of changing trends in conservation science and advances in foundational technologies, including genomics and geospatial science. Multispecies approaches may provide more fundamental insights into evolutionary processes and equip managers with a more holistic understanding of the landscapes under their jurisdiction. Central to this approach are data generation and analyses which embrace and reflect a broad range of taxonomic diversity. Here, we examine the family-level phylogenetic breadth of the California Conservation Genomics Project (CCGP) based on family-level phylogenetic diversity (PD), family-level phylogenetic distinctness, and family richness. We place this in the context of the diversity present in California and compare it to the 35-plus years of genetic research compiled in the CaliPopGen Database. We found that the family-level PD in the CCGP reflected that of California very well, slightly overrepresenting chordates and underrepresenting arthropods, and that 42% of CCGP PD represented new contributions to genetic data for the state. In one focused effort, the CCGP was able to achieve roughly half the family-level PD studied over the last several decades. To maximize studied PD, future work should focus on arthropods, a conclusion that likely reflects the overall lack of attention to this hyperdiverse clade.
Coarse judgment: patent for abrasive material invalidated on the grounds of ‘undue burden’
Authors: Strath Janet
Published: September 2022

The Patents Court has held that a European Patent covering dish-shaped abrasive particles is invalid because it would require an undue burden to produce particles across the scope of the claims.
Direct and Indirect Impacts of the Tuberolachnus salignus (Hemiptera: Aphididae) Invasion in New Zealand and Management Alternatives
Authors: Tun Kyaw Min , Minor Maria , Jones Trevor , Clavijo McCormick Andrea
Published: September 2022

Invasive insects are a serious problem in New Zealand, and their introduction and successful establishment are predicted to increase with global commerce and climate change. A recent introduction to New Zealand is Tuberolachnus salignus (Gmelin), a large aphid that attacks mainly willows but also other plants such as poplars, apples, and pears. It was first reported in 2013 but has since then spread rapidly throughout the country. We conducted a 2-yr study exploring the direct (on the host plant) and indirect (on other organisms) impacts of the aphid, in a field setting including 15 willow clones selected to represent the variety of species and hybrids present in New Zealand. Our research revealed great variation in the level of resistance/susceptibility of different clones and suggested a trade-off between reproduction, growth, and defense. We investigated the indirect effects of the aphid on honeydew foragers and on the soil ecosystem, through honeydew production and deposition, revealing complex cascading effects involving multiple trophic levels. We also explore and discuss management alternatives including the replacement of willows for native species or resistant varieties, the use of biological control agents, and the feasibility of chemical control. This work is one of few studies on the complex ecological effects of invasive phytophagous insects and could serve as a model for future research and to inform pest management. To conclude, we identify gaps in the knowledge and highlight aspects requiring further research.
Current perspectives of the Japanese Esophageal Oncology Group on the development of immunotherapy for esophageal cancer
Authors: Kadono Toru , Yamamoto Shun , Kato Ken
Published: September 2022

Esophageal cancer is the seventh most common cancer worldwide and continues to have a poor prognosis. Starting with the development of immune checkpoint inhibitors for patients with metastatic melanoma, many clinical trials have been conducted to evaluate the efficacy and safety of immune checkpoint inhibitors against various malignancies. Although few effective drugs are available for patients with advanced esophageal cancer, two immune checkpoint inhibitors, nivolumab and pembrolizumab, have been approved as second-line treatments for advanced esophageal squamous cell carcinoma. Recently, immune checkpoint inhibitors have shown promising results as post-operative therapies and first-line treatments for advanced esophageal cancer. Nivolumab has been approved as a post-operative therapy based on the CheckMate-577 trial, and nivolumab, ipilimumab and pembrolizumab have been approved as first-line treatments based on the CheckMate-648 trial and the KEYNOTE-590 trial. In addition, many trials of immune checkpoint inhibitors plus pre-operative treatment or definitive chemoradiotherapy are ongoing. The Japan Esophageal Oncology Group was established in 1978 and has conducted numerous clinical trials, most of which have examined multimodality treatments. In the era of immunotherapy, Japan Esophageal Oncology Group is conducting a clinical trial studying multimodality treatment with an immune checkpoint inhibitor. JCOG1804E (FRONTiER) is a phase I trial to evaluate the safety and efficacy of nivolumab plus pre-operative chemotherapy followed by surgery. These results might improve the clinical outcomes of esophageal cancer patients.
A multicentre retrospective study comparing site-specific treatment with empiric treatment for unfavourable subset of cancer of unknown primary site
Authors: Nishikawa Kazuo , Hironaka Shuichi , Inagaki Takashi , Komori Azusa , Otsu Satoshi , Mitsugi Kenji , Makiyama Akitaka , Watanabe Koichiro , Tamura Shingo , Okumura Yuta , Kusaba Hitoshi , Esaki Taito , Baba Eishi , Shirao Kuniaki
Published: September 2022

Background

Patients with cancer of unknown primary site are divided into two distinct groups, favourable and unfavourable subsets. For the unfavourable subset, empiric treatment or site-specific treatment is recommended, but limited knowledge exists about the efficacy of site-specific treatment compared with empiric treatment in clinical practice.

Methods

In this multicentre retrospective study, we reviewed the medical records of patients with cancer of unknown primary site treated with chemotherapy (or chemoradiotherapy) as first-line treatment from eight institutions during 2006–18. We investigated the workup modality and categorized the patients into favourable and unfavourable subsets, which were further divided into site-specific and empiric treatment groups. Site-specific treatment is defined as a standard chemotherapy for an estimated primary site. We examined the efficacy in the favourable and unfavourable subsets and performed multivariable analysis for estimating the overall survival in the unfavourable subset.

Results

Of 177 patients with cancer of unknown primary site, 33 and 144 were categorized into favourable and unfavourable subsets, respectively. In the unfavourable subset, 84 patients (58.3%) received empiric therapy, and 60 patients (41.7%) received site-specific treatment. Median overall survival was 10.0 and 10.1 months in site-specific and empiric treatment groups, respectively, with no significant difference (hazard ratio 1.01, 95% confidence interval 0.70–1.45, P = 0.95). Multivariable analysis revealed performance status, number of metastatic sites and hypoalbuminaemia as independent prognostic factors for overall survival in the unfavourable subset.

Conclusions

Overall survival in site-specific and empiric treatment groups was similar in the unfavourable cancer of unknown primary site subset in this study. Further research is needed to prolong overall survival in patients in the unfavourable cancer of unknown primary site subset.
Red Rubiscos and opportunities for engineering green plants
Authors: Oh Zhen Guo , Askey Bryce , Gunn Laura H
Published: September 2022

Nature’s vital, but notoriously inefficient, CO2-fixing enzyme Rubisco often limits the growth of photosynthetic organisms including crop species. Form I Rubiscos comprise eight catalytic large subunits and eight auxiliary small subunits and can be classified into two distinct lineages—‘red’ and ‘green’. While red-type Rubiscos (Form IC and ID) are found in rhodophytes, their secondary symbionts, and certain proteobacteria, green-type Rubiscos (Form IA and IB) exist in terrestrial plants, chlorophytes, cyanobacteria, and other proteobacteria. Eukaryotic red-type Rubiscos exhibit desirable kinetic properties, namely high specificity and high catalytic efficiency, with certain isoforms outperforming green-type Rubiscos. However, it is not yet possible to functionally express a high-performing red-type Rubisco in chloroplasts to boost photosynthetic carbon assimilation in green plants. Understanding the molecular and evolutionary basis for divergence between red- and green-type Rubiscos could help us to harness the superior CO2-fixing power of red-type Rubiscos. Here we review our current understanding about red-type Rubisco distribution, biogenesis, and sequence–structure, and present opportunities and challenges for utilizing red-type Rubisco kinetics towards crop improvements.
Religious Experience, Storytelling, and Ethical Action in Muhammad Iqbal’s Javid Nama and Gotthold Ephraim Lessing’s Nathan
Authors: Khan Maria , Wagner Ulrike
Published: September 2022

This article brings Muhammad Iqbal’s Persian book of poetry, Javid Nama, into dialogue with Gotthold Ephraim Lessing’s drama Nathan the Wise. In conversation with Islam’s early history, narrative traditions, and debates over the status of revelation and reason, both authors, we argue, envision religious truth as an irreducible experience that no single doctrine can lay exclusivist claims to. We demonstrate that intuition, reason, and revelation coexist as different paths toward spiritual insights in their fictional works. In different yet comparable ways, they create a fresh ontological ground for negotiating questions of divine truth and move the searching subject centre stage. Focused on deeds and actions, their reform projects promote an ethical conduct of life and acceptance among different religious groups that could not contrast more profoundly with the political reality in most Islamic countries today.
WR 63: a multiple system (O+O) + WR?
Authors: Chené André-Nicolas , Mahy Laurent , Gosset Eric , St-Louis Nicole , Dsilva Karan , Manick Rajeev
Published: September 2022

The spectrum of the Wolf–Rayet (WR) star WR 63 contains spectral lines of two different O stars that show regular radial velocity (RV) variations with amplitudes of ∼160 and ∼225 km s−1 on a ∼4.03 d period. The light curve shows two narrow eclipses that are 0.2 mag deep on the same period as the RV changes. On the other hand, our data show no significant RV variations for the WR spectral lines. Those findings are compatible with WR 63 being a triple system composed of two non-interacting late-O stars orbiting a WR star on a period longer than 1000 d. The amplitude of the WR spectral line-profile variability reaches 7–8 per cent of the line intensity and seems related to a 0.04 mag periodic photometric variation. Large wind density structures are a possible origin for this variability, but our data are not sufficient to verify this. Our analysis shows that, should the three stars be bound, they would be coeval with an age of about 5.9 ± 1.4 Myr. The distance to the O stars is estimated to be $3.4\, \pm \, 0.5$ kpc. Their dynamical masses are 14.3 ± 0.1 and 10.3 ± 0.1 M⊙. Using rotating single-star evolutionary tracks, we estimate their initial masses to be 18 ± 2 and 16 ± 2 M⊙ for the primary and the secondary, respectively. Regular spectral monitoring is required in the future to detect RV variations of the WR star that would prove that it is gravitationally bound to the close O+OB system and to determine its mass.
Search and identification of transient and variable radio sources using MeerKAT observations: a case study on the MAXI J1820+070 field
Authors: Rowlinson A , Meijn J , Bright J , van der Horst A J , Chastain S , Fijma S , Fender R , Heywood I , Wijers R A M J , Woudt P A , Andersson A , Sivakoff G R , Tremou E , Driessen L N
Published: September 2022

Many transient and variable sources detected at multiple wavelengths are also observed to vary at radio frequencies. However, these samples are typically biased towards sources that are initially detected in wide-field optical, X-ray, or gamma-ray surveys. Many sources that are insufficiently bright at higher frequencies are therefore missed, leading to potential gaps in our knowledge of these sources and missing populations that are not detectable in optical, X-rays, or gamma-rays. Taking advantage of new state-of-the-art radio facilities that provide high-quality wide-field images with fast survey speeds, we can now conduct unbiased surveys for transient and variable sources at radio frequencies. In this paper, we present an unbiased survey using observations obtained by MeerKAT, a mid-frequency (∼GHz) radio array in South Africa’s Karoo Desert. The observations used were obtained as part of a weekly monitoring campaign for X-ray binaries (XRBs) and we focus on the field of MAXI J1820+070. We develop methods to efficiently filter transient and variable candidates that can be directly applied to other data sets. In addition to MAXI J1820+070, we identify four likely active galactic nuclei, one source that could be a Galactic source (pulsar or quiescent XRB) or an AGN, and one variable pulsar. No transient sources, defined as being undetected in deep images, were identified leading to a transient surface density of <3.7 × 10−2 deg−2 at a sensitivity of 1 mJy on time-scales of 1 week at 1.4 GHz.
ExoMol line lists – XLVII. Rovibronic molecular line list of the calcium monohydroxide radical (CaOH)
Authors: Owens Alec , Mitrushchenkov Alexander , Yurchenko Sergei N , Tennyson Jonathan
Published: September 2022

Any future detection of the calcium monohydroxide radical (CaOH) in stellar and exoplanetary atmospheres will rely on accurate molecular opacity data. Here, we present the first comprehensive molecular line list of CaOH covering the $\tilde{A}\, ^2\Pi$–$\tilde{X}\, ^2\Sigma ^+$ rotation-vibration-electronic and $\tilde{X}\, ^2\Sigma ^+$–$\tilde{X}\, ^2\Sigma ^+$ rotation-vibration bands. The newly computed OYT6 line list contains over 24.2 billion transitions between 3.2 million energy levels with rotational excitation up to J = 175.5. It is applicable to temperatures up to T = 3000 K and covers the 0–35 000 cm−1 range (wavelengths λ > 0.29 μm) for rotational, rotation-vibration and the $\tilde{A}\, ^2\Pi$–$\tilde{X}\, ^2\Sigma ^+$ electronic transitions. The strong band around 16 000 cm−1 (λ = 0.63 μm) is likely to be of interest in future astronomical observations, particularly in hot rocky exoplanets where temperatures can become extremely high. The OYT6 line list has been generated using empirically refined $\tilde{X}\, ^2\Sigma ^+$ and $\tilde{A}\, ^2\Pi$ state potential energy surfaces, high-level ab initio transition dipole moment surfaces, and a rigorous treatment of both Renner–Teller and spin-orbit coupling effects, which are necessary for correctly modelling the CaOH spectrum. Post-processing of the CaOH line list has been performed so as to tailor it to high-resolution applications, i.e. by replacing calculated energy levels with more accurate empirically derived values (where available), hence improving the accuracy of the predicted line positions in certain regions. The OYT6 line list is available from the ExoMol data base at www.exomol.com and the CDS astronomical data base.
Evidence of galaxy assembly bias in SDSS DR7 galaxy samples from count statistics
Authors: Wang Kuan , Mao Yao-Yuan , Zentner Andrew R , Guo Hong , Lange Johannes U , van den Bosch Frank C , Mezini Lorena
Published: September 2022

We present observational constraints on the galaxy–halo connection, focusing particularly on galaxy assembly bias from a novel combination of counts-in-cylinders statistics, P(NCIC), with the standard measurements of the projected two-point correlation function wp(rp), and number density ngal of galaxies. We measure ngal, wp(rp), and P(NCIC) for volume-limited, luminosity-threshold samples of galaxies selected from SDSS DR7, and use them to constrain halo occupation distribution (HOD) models, including a model in which galaxy occupation depends upon a secondary halo property, namely halo concentration. We detect significant positive central assembly bias for the Mr < −20.0 and Mr < −19.5 samples. Central galaxies preferentially reside within haloes of high concentration at fixed mass. Positive central assembly bias is also favoured in the Mr < −20.5 and Mr < −19.0 samples. We find no evidence of central assembly bias in the Mr < −21.0 sample. We observe only a marginal preference for negative satellite assembly bias in the Mr < −20.0 and Mr < −19.0 samples, and non-zero satellite assembly bias is not indicated in other samples. Our findings underscore the necessity of accounting for galaxy assembly bias when interpreting galaxy survey data, and demonstrate the potential of count statistics in extracting information from the spatial distribution of galaxies, which could be applied to both galaxy–halo connection studies and cosmological analyses.
Multiple flares caused by mass ejection episodes during the advanced nebular phase of Nova Scuti 2019
Authors: Munari U , Righetti G L , Dallaporta S
Published: September 2022

Our photometric and spectroscopic monitoring shows that starting with 2020 June 4, day  +217 from optical maximum and well into its advanced nebular stage, Nova Scuti (Nova Sct) 2019 begun displaying a series of nine large amplitude flares (up to $\Delta m \sim 1.7$ mag), characterized by a rapid rise to peak (≤10 h) and a fast exponential decline (e-folding time ∼50 h). The time interval Δt between flares follows an ordered sequence, declining from 8.43 to 4.90 d, that safely allows to exclude that any other flare occurred without being recorded by the observations. When the sequence of flares was over by 2020 July 28 (day  +271), Nova Sct 2019 slowed its overall decline rate from Δm = 0.0067 to 0.0027 mag d−1. The flares were caused by material expelled at high velocity (∼1000 km s−1) from the still burning white dwarf (WD). The cooler pseudo-photosphere forming at each flare in the expelled material, resulted in a recombination wave to spread through the original nova ejecta (at ∼170 au from the WD), quenching emission from [Fe x] and [Fe vii] and boosting that from lower ionization species. After each flare, once the small amount of expelled material had turned optically thin, the original nova ejecta resumed displaying [Fe x] and [Fe vii] emission lines, a fact that clearly proves the direct photoionization action exerted on the ejecta by the burning WD. While the other known flaring novae (V458 Vul, V4745 Sgr, and V5588 Sgr) presented the flares close to maximum brightness and with increasing Δt, Nova Sct 2019 is unique in having displayed them during the advanced nebular stage and with decreasing Δt.
Impact of magnetic fields on Population III star formation
Authors: Saad Cynthia R , Bromm Volker , El Eid Mounib
Published: September 2022

The theory of the formation of the first stars in the Universe, the so-called Population III (Pop III), has until now largely neglected the impact of magnetic fields. Complementing a series of recent studies of the magnetohydrodynamic (MHD) aspects of Pop III star formation, we here carry out a suite of idealized numerical experiments where we ascertain how the fragmentation properties of primordial protostellar discs are modified if MHD effects are present. Specifically, starting from cosmological initial conditions, we focus on the central region in a select minihalo at redshift z ∼ 25, inserting a magnetic field at an intermediate evolutionary stage, normalized to a fraction of the equipartition value. To explore parameter space, we consider different field geometries, including uniform, radial, toroidal, and poloidal field configurations, with the toroidal configuration being the most realistic. The collapse of the gas is followed for ∼8 orders of magnitude in density after the field was inserted, until a maximum of $10^{15} {\rm \, cm}^{-3}$ is reached. We find that the magnetic field leads to a delay in the collapse of the gas. Moreover, the toroidal field has the strongest effect on the collapse as it inhibits the fragmentation of the emerging disc surrounding the central core and leads to the formation of a more massive core. The full understanding of the formation of Pop III stars and their mass distribution thus needs to take into account the effect of magnetic fields. We further conclude that ideal MHD is only a first step in this endeavour, to be followed up with a comprehensive treatment of dissipative effects, such as ambipolar diffusion and Ohmic dissipation.
Common envelopes in massive stars II: The distinct roles of hydrogen and helium recombination
Authors: Lau Mike Y M , Hirai Ryosuke , Price Daniel J , Mandel Ilya
Published: September 2022

The role of recombination during a common-envelope event has been long debated. Many studies have argued that much of hydrogen recombination energy, which is radiated in relatively cool and optically thin layers, might not thermalize in the envelope. On the other hand, helium recombination contains ≈30 per cent of the total recombination energy, and occurs much deeper in the stellar envelope. We investigate the distinct roles played by hydrogen and helium recombination in a common-envelope interaction experienced by a 12 $\, \rm {M}_{\odot }$ red supergiant donor. We perform adiabatic, 3D hydrodynamical simulations that (i) include hydrogen, helium, and H2 recombination, (ii) include hydrogen and helium recombination, (iii) include only helium recombination, and (iv) do not include recombination energy. By comparing these simulations, we find that the addition of helium recombination energy alone ejects 30 per cent more envelope mass, and leads to a 16 per cent larger post-plunge-in separation. Under the adiabatic assumption, adding hydrogen recombination energy increases the amount of ejected mass by a further 40 per cent, possibly unbinding the entire envelope, but does not affect the post-plunge separation. Most of the ejecta becomes unbound at relatively high (>70 per cent) degrees of hydrogen ionisation, where the hydrogen recombination energy is likely to expand the envelope instead of being radiated away.