bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome of adalimumab monotherapy in paediatric non-infectious uveitis
Authors: Al-Julandani Dalila Ali , Bagri Narendra , Tsang Nakita , Clark Sarah , Upadhyay Ashish Datt , Guly Catherine , Ramanan Athimalaipet
Published: December 2022

Background: Adalimumab in combination with other disease-modifying drugs (DMARD) such as methotrexate has a proven efficacy in the management of paediatric non-infectious uveitis. However, many children experience significant intolerance to methotrexate while on this combination, leaving a dilemma for clinicians for choosing the subsequent therapeutic roadmap. Continuation of adalimumab monotherapy might be an alternative feasible option under such settings. This study aims to investigate the efficacy of adalimumab monotherapy in paediatric non-infectious uveitis.
Methods: Children with non-infectious uveitis on adalimumab monotherapy (from August 2015 to June 2022) following intolerance to accompanying methotrexate or mycophenolate mofetil were included in this retrospective study. Data was collected at initiation of adalimumab monotherapy and at three monthly intervals until the last visit. Primary outcome was to evaluate disease control on adalimumab monotherapy as determined by the proportion of patients who had less than a 2-step worsening in uveitis (as per SUN score) and no additional systemic immunosuppression during follow-up. Secondary outcome measures were visual outcome, complications and side-effect profile of adalimumab monotherapy.
Results: Data was collected for 28 patients (56 eyes). The most common uveitis type and course were anterior and chronic uveitis respectively. Juvenile idiopathic arthritis associated uveitis was the most common underlying diagnosis. During the study period 23 (82, 14%) of the study subjects met the primary outcome. On Kaplan-Meier survival analysis 81.25% (95% CI; 60.6-91.7%) children maintained remission at 12 months of on adalimumab monotherapy.
Conclusion: Continuation of adalimumab monotherapy is an effective therapeutic option for the treatment of non-infectious uveitis in children who are intolerant to the combination of adalimumab and methotrexate or mycophenolate.
Thermodynamical framework for effective mitigation of high aerosol loading in the Indo-Gangetic Plain during winter
Authors: Acharja Prodip , Ghude Sachin D. , Sinha Baerbel , Barth Mary , Kulkarni Rachana , Sinha Vinayak , Kumar Rajesh , Ali Kaushar , Govardhan Gaurav , Gultepe Ismail , Rajeevan Madhavan Nair
Published: December 2022

The Indo-Gangetic Plain (IGP) experiences severe air pollution every winter, with ammonium chloride and ammonium nitrate as the major inorganic fractions of fine aerosols. Many past attempts to tackle air pollution in the IGP were inadequate, as they targeted a subset of the primary pollutants in an environment where the majority of the particulate matter burden is secondary in nature. Here, we provide new mechanistic insight into aerosol mitigation by integrating the ISORROPIA-II thermodynamical model with high-resolution simultaneous measurements of precursor gases and aerosols. A mathematical framework is explored to investigate the complex interaction between hydrochloric acid (HCl), nitrogen oxides (NOx), ammonia (NH3), and aerosol liquid water content (ALWC). Aerosol acidity (pH) and ALWC emerge as governing factors that modulate the gas-to-particle phase partitioning and mass loading of fine aerosols. Six "sensitivity regimes" were defined, where PM1 and PM2.5 fall in the "HCl and HNO3 sensitive regime", emphasizing that HCl and HNO3 reductions would be the most effective pathway for aerosol mitigation in the IGP, which is ammonia-rich during winter. This study provides evidence that precursor abatement for aerosol mitigation should not be based on their descending mass concentrations but instead on their sensitivity to high aerosol loading.
Non diabetic renal disease in the diabetic: Pilot study
Authors: Weerakkody Ranga , Ginige Anusha , Ranathunge Niluka
Published: December 2022

Diabetes is the most important factor for chronic renal failure. Studies have shown that patients with diabetes could have non diabetic kidney disease as coexisting pathologies in up to 1/3 of patients with diabetic nephropathy. The status of Sri Lanka is not known and this pilot study was done to find the prevalence of non-diabetic kidney disease. This is a retrospective study done by analyzing biopsy reports and patient data. The commonest non diabetic kidney disease was hypertensive nephrosclerosis, followed up by membranoproliferative glomerulonephritis. 26.9% had non-diabetic kidney disease and 1/3 of them have a potentially curable condition with immunosuppression.
Chaos Raman distributed optical fiber sensing
Authors: Zhang Mingjiang , Wang Chenyi , Li Jian , Zhou Xinxin , Cheng Zijia , Qiao Lijun , Xue Xiaohui
Published: December 2022

The physics principle of pulse flight positioning is the main theoretical bottleneck that restricts the spatial resolution of the existing Raman distributed optical fiber sensing scheme. Owing to the pulse width of tens of nanoseconds, the spatial resolution of the existing Raman distributed optical fiber sensing scheme with kilometer-level sensing distance is limited to the meter level, which seriously restricts the development of the optical time-domain reflection system. In this paper, a chaos laser is proposed in the context of the physical principle of the Raman scattering effect, and a novel theory of chaos Raman distributed optical fiber sensing scheme is presented. The scheme reveals the characteristics of chaos Raman scattering light excited by a chaotic signal on the sensing fiber. Further, the chaos time-domain compression demodulation mechanism between the temperature variation information and chaos correlation peak is demonstrated. Then, the position of the temperature variation signal is precisely located using the delay time of the chaos correlation peak combined with the chaos pulse flight time. Based on this novel optical sensing mechanism, an experiment with 10 cm spatial resolution and 1.4 km sensing distance was conducted, and the spatial resolution was found to be independent of the sensing distance. Within the limit of the existing spatial resolution theory, the spatial resolution of the proposed scheme is 50 times higher than that of the traditional scheme. The scheme also provides a new research direction for optical chaos and optical fiber sensing.
Amplicon-based metagenomic association analysis of gut microbiota in relation to egg-laying period and breeds of hens
Authors: Wang Xiangyu , Meng Jin-Xin , Ren Wei-Xin , Ma He , Liu Gang , Liu Rui , Geng Hong-Li , Zhao Quan , Zhang Xiao-Xuan , Ni Hong-Bo
Published: December 2022

Background
Gut microbiota plays a vital role in the maintenance of gut homeostasis and the improvement of performance. The gut microbiota of laying hens is visibly different in different laying stages, which correlates significantly with egg production. To better understand the association between characteristics of microbial community and different laying periods in Hyland brown and Isa laying hens, we conducted a 16S rRNA amplicon sequencing survey.
Results
Our result revealed the diversity of bacteria in the early laying period was commonly higher than peak, and in Hyland brown laying hens were generally higher than Isa. Principal coordinate analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA) revealed that the structure and composition of the gut microbiota of laying hens exhibited significant differences among different groups. Phylum Firmicutes, Bacteroidota, Proteobacteria, and Fusobacteriota were found that dominated in the host’s feces. Therein, the abundance of Fusobacteriota was higher in the peak period than in the early period, while the abundance of Cyanobacteria in the early period was higher in two breeds of hens. Furthermore, random forest based on machine learning showed that there were several distinctly abundant genera, which can be used as potential biomarkers to differentiate the different groups of laying periods and breeds. In addition, the prediction of biological function indicated the existing discrepancy in microbial function among the microbiota of four groups.
Conclusions
Our findings provide new insights for understanding the bacterial diversity and intestinal flora composition of different strains of laying hens during different laying periods, and contributed beneficially to improving the production performance of laying hens and preventing chicken diseases.
Assessing Knowledge and Barriers at the Primary Care Provider Level that Contribute to Disparities in Inflammatory Breast Cancer Diagnosis and Treatment
Authors: Devi Gayathri , Fish Laura , Bennion Alexandra , Sawin Gregory , Weaver Sarah , Tran Anh
Published: December 2022

Purpose: The purpose of this study was to evaluate knowledge gaps and barriers related to diagnosis and care of inflammatory breast cancer (IBC), a rare but most lethal breast cancer subtype, amongst Primary Care Providers (PCP) as they are often the first point of contact when patients notice initial symptoms.
Methods: PCP participants within Duke University Health System, federally qualified health center, corporate employee health and community practices, nearby academic medical center, Duke physician assistant, and nurse leadership program alumni were first selected in a convenience sample (n=11) for semi-structured interviews (n=11). Based on these data, an online survey tool was developed and disseminated (n=78) to assess salient measures of IBC diagnosis, health disparity factors, referral and care coordination practices, COVID impact, and continued medical education (CME).
Results: PCP reported access to care and knowledge gaps in symptom recognition (mean = 3.3, range 1-7) as major barriers. Only 31% reported ever suspecting IBC in a patient. PCP (n=49) responded being challenged with referral delays in diagnostic imaging. Additionally, since the COVID-19 pandemic started, 63% reported breast cancer referral delays, and 33% reported diagnosing less breast cancer. PCP stated interest in CME in their practice for improved diagnosis and patient care, which included online (53%), lunch time or other in-service training (33%), patient and provider-facing websites (32%).
Conclusions: Challenges communicating rare cancer information, gaps in confidence in diagnosing IBC, and timely follow-up with patients and specialists underscores the need for developing PCP educational modules to improve guideline-concordant care.
Unbiased Image Segmentation Assessment Toolkit for Quantitative Differentiation of State-of-the- Art Algorithms and Pipelines
Authors: Goyal Vishakha , Schaub Nick J. , Voss Ty C. , Hotaling Nathan A.
Published: December 2022

Background
Image segmentation pipelines are commonly used in microscopy to identify cellular compartments like nucleus and cytoplasm, but there are few standards for comparing segmentation accuracy across pipelines. The process of selecting a segmentation pipeline can seem daunting to researchers due to the number and variety of metrics available for evaluating segmentation accuracy.
Results
Here we present automated pipelines to obtain a comprehensive set of 69 metrics to evaluate segmented data and propose a selection methodology for models based on quantitative analysis, dimension reduction or unsupervised classification techniques and informed selection criteria.
Conclusion
We show that the metrics used here can often be reduced to a small number of metrics that give a more complete understanding of segmentation accuracy, with different groups of metrics providing sensitivity to different types of segmentation error. These tools are delivered as easy to use python libraries, command line tools, Common Workflow Language Tools, and as Web Image Processing Pipeline interactive plugins to ensure a wide range of users can access and use them. We also present how our evaluation methods can be used to observe the changes in segmentations across modern machine learning/deep learning workflows and use cases.
Efficacy of antiandrogens in androgen receptor-positive triple-negative metastatic breast cancer: real-life data
Authors: RHANINE Yasmine , BONNEFOI Hervé , GONCALVES Anthony , DEBLED Marc , Moulec Sylvestre Le , BONICHON Nathalie , MACGROGAN Gaetan , ARNEDOS Monica , DUBROCA-DEHEZ Bénédicte , Grellety Thomas
Published: December 2022

Purpose
Androgen Receptor (AR) + triple-negative breast cancer (TNBC) accounts for approximately 25% of all TNBC. Several trials using different antiandrogens (AA) found clinical benefit rates (CBR) ranging from 19 to 29%. The aim of this retrospective trial was to assess the clinical benefit of AA in real life.
Methods
Patients with metastatic AR + TNBC who have received at least one dose of an AA (abiraterone acetate, enzalutamide or bicalutamide) were eligible. Assessable patients received at least 4 weeks of AA and at least one tumor assessment. The primary end-point was CBR at 6 months defined as patients exhibiting an objective response (OR) or stable disease (SD) for at least 6 months.
Results
A total of 26 patients were eligible and 24 patients were assessable. Median age at initiation of AA was 70 years (range 50–90). Fifty percent exhibited liver and/or lung metastases. Median number of previous lines of chemotherapy was 3 (range 0–10). AA used were: abiraterone acetate (62%), enzalutamide (8%) and bicalutamide (30%). CBR at 6 months was 29% (7/24) with 5 OR (2 CR, 3 PR) and 2 SD. Fifty-seven percent (4/7) of patients with a 6-months CBR received AA in first line versus 18% (3/17) in later lines. Four patients had a clinical benefit > 12 months. There were no grade > 2 side effects.
Conclusion
Real-life efficacy of AA use in metastatic AR + TNBC are in line with data from published trials. A proportion of AR + TNBC patients benefit from AA and with some deriving long-term clinical benefit.
Cited1 as a Marker of Favourable Outcome in Anti-endocrine Treated Erα-positive, Lymph Node Negative Breast Cancer
Authors: Dahlgren Malin , Lettiero Barbara , Dalal Hina , Mårtensson Kira , Gaber Alexander , Nodin Björn , Gruvberger-Saal Sofia K. , Saal Lao H. , Howlin Jillian
Published: December 2022

OBJECTIVE: We present our observations of CITED1 as a potential biomarker of anti-endocrine treatment response and recurrence in breast cancer and suggest that this is dependent on its role in mediating a specific ERα transcriptional response. The study is a continuation of earlier work establishing the role of CITED1 in mammary gland development.
RESULTS: CITED1 mRNA is associated with ER-positivity and selectively expressed in the GOBO dataset of cell lines and tumours representing the luminal-molecular subtype. In patients treated with tamoxifen, higher CITED1 correlated with better outcome, suggesting a role in anti-estrogen treatment response. The effect was particularly evident in the subset of ER+, lymph node negative patients and noticeable divergence of the groups was apparent only after at least 5 years. TMA analysis further validated the association of CITED1 protein, by IHC, with favourable outcome in ER+, tamoxifen-treated tumours. Although we also found a favourable response to anti-endocrine treatment in a larger TCGA dataset, the tamoxifen-specific effect was not replicated. MCF7s overexpressing CITED1 showed selective amplification of AREG but not TGFαsuggesting that maintenance of specific ERα-CITED1 mediated transcription is important for the long-term response to anti-endocrine therapy and that CITED1 could potentially be utilized as a prognostic biomarker.
Drug exposure during pregnancy: A case-control study of abortions of a Catalan Primary Care Database
Authors: Gomez-Lumbreras Ainhoa , Vazquez Marta Leston , Vilaplana-Carnerero Carles , Prat-Vallverdu Oriol , Vedia Cristina , Morros Rosa , Giner-Soriano Maria
Published: December 2022

Background: Exposure to medicines during pregnancy is frequent, even more during first trimester as pregnant women might not be aware of their condition. Aiming to establish potential relationship of earlier exposure to medicines and risk of abortion we conducted an observational study.
Methods: this is a retrospective case-control study of abortions (cases) and live birth pregnancies (controls) matched by mother age using SIDIAP database (Catalan Primary Health electronic health records database). Exposure to medicines while pregnant was considered to assess the risk of abortion during the first trimester. The odds ratio was estimated by a conditional logistic regression and adjust by health conditions and medicines exposures.
Results: A total of 60,350 episodes of abortions were matched to 118,085 live birth/completed pregnancy episodes. Cases had higher rates of alcohol intake (9.9% vs 7.2%), smoking (4.5% vs 3.6%) and of previous abortions (9.9% vs 7.8%). Anxiety (30.3% and 25.1%), respiratory diseases (10.6% and 9.2%) and migraine (8.2% and 7.3%), for cases and controls respectively, were the most frequent baseline conditions. Cases had higher rate of exposure to medicines [40,148 (66.5%) vs 37636 (68.9%), p<0.001, cases and controls respectively]. A risk for abortion was found for antihistamines for systemic use (ORadj 1.23, 95%CI 1.19-1.27), antidepressants (ORadj 1.11, 95%CI 1.06-1.17), anxiolytics (ORadj 1.31, 95%CI 1.26-1.73), and anti-inflammatory and rheumatic products, non-steroids (ORadj 1. 63, 95%CI 1.59-1.67).
Conclusions: These highest rate of medicines exposures during the first trimester of pregnancy and their relationship with abortion highlights the relevance of prescription to women with childbearing potential and may lead to better family planning information and contraception plans.
Registration: EUPAS37675
Experience Exceeds Awareness of Anthropogenic Climate Change in Greenland
Authors: Minor Kelton , Lund-Jensen Manumina , Hamilton Lawrence , Bendixen Mette , Lassen David Dreyer , Rosing Minik
Published: December 2022

Greenland’s residents and Ice Sheet are both exposed to pronounced Arctic warming. Although Greenland is a hub for climate science, the climate perceptions of Greenland’s predominantly Indigenous population remained unstudied through the past decade of multi-national climate opinion polls. Conducting two original nationally representative surveys, here we show that Greenlanders are more likely than residents of top oil-producing Arctic countries to perceive that climate change is happening, and about twice as likely to have personally experienced its effects. However, half are unaware that climate change is human-caused, and those who are most affected appear to be least aware. An Inuit cultural dimension, indicated by the intertwined social ecological factors of Indigenous identity, subsistence occupation, village community scale and no post-elementary education, proves to be the main positive predictor of climate change experience but also the strongest negative predictor of awareness of human-caused climate change. Despite Greenland’s centrality to climate research, we uncover a widespread gap between the scientific consensus and coastal Kalaallit views of climate change, particularly among the country’s youth, fishers, and hunters. This science-society gulf has immediate and prospective implications for local climate adaptation, climate science communication and knowledge exchange between generations, institutions, and communities.
Livelihood Challenges of Single Female Household Heads in the Rohingya and Host Communities in Cox’s Bazar, Bangladesh during the COVID-19 Pandemic
Authors: Nasar Sameen , Nadim A.S.M. , Raz Saifa , Jabbar Abdul , Hossain Muhammad Riaz , Aktar Bachera , Rahman M Shafiqur , Rashid Sabina Faiz
Published: December 2022

Background
Following the mass influx of Rohingya refugees into Cox’s Bazaar, Bangladesh in 2017, makeshift settlement camps in Ukhiya and Teknaf have been overburdened, leading to livelihood challenges for both Rohingya and host communities. The humanitarian crisis has had adverse effects on vulnerable populations, which include the elderly, persons with disabilities, adolescents, and single female household heads. Using a subset of a larger dataset on households with most vulnerable groups in both communities, we analysed the effect of the pandemic and lockdown on the livelihood of single female household (HH) heads.
Methods
A cross-sectional household roster survey was designed to collect data from households with most vulnerable groups (MVGs) of host and Rohingya communities from December 2020 to March 2021; 11 host community villages and 10 Rohingya camps purposively selected as per the affiliated intervention of the project. The paper analysed quantitative and qualitative data from the sub-group of single female household heads without no income/low income. Participants were surveyed for their socio-demographic characteristics, COVID-19 experiences and knowledge, and food security situation, social experiences and mental health.
Results
We surveyed 432 single female HH heads. Support during the pandemic was reported to be low, with less than 50% of HHs reporting relief meeting their needs; only 36% and 15% of these HHs received rations in camps and host communities respectively. Loan facilities were mostly unavailable and there were reported insufficiencies in food consumption. Over 50% of respondents tested positive on the PHQ-2. Further analyses indicates that having a chronic health issue (OR 2.2, 95% CI 1.33–3.66) was positively associated with the PHQ-2 score Rohingya single females. For host single females, having an ill member in the HH (OR 1.46, 95% CI 1.02–2.08) and the inability to save before the pandemic (OR 1.57 95% CI 1.11–2.23) increased the odds of testing positive.
Conclusion
Our study findings revealed insufficiencies with economic opportunities and food security for single female headed households, as well as a high rate of positive screening for depression amongst this population. These findings call for a more in-depth understanding of the needs of this group.
Cognitive Impairments Predict the Behavioral and Psychological Symptoms of Dementia
Authors: Hemrungrojn Solaphat , Tangwongchai Sookjaroen , Charernboon Thammanard , Phanasathit Muthita , Chaipresertsud Pisit , Maleevach Pacharaporn , Likitjaroen Yuttachai , Phanthumchinda Kammant , Assawatinna Ratiya , Amrapala Arisara , Maes Michael
Published: December 2022

Background: To evaluate the association between behavioral and psychological symptoms of dementia (BPSD), as assessed via the Neuropsychiatric Inventory Questionnaire (NPI-Q), and cognitive impairments in individuals with dementia and amnestic mild cognitive impairment (aMCI).Methods:120 participants, comprising of 80 aMCI and 40 Alzheimer’s disease (AD) subjects, were included in the study. aMCI was diagnosed using Petersen’s criteria, whilst AD was diagnosed using the National Institute of Neurological and Communicative Disorders and Stroke/AD criteria.Results:Pure exploratory bifactor analysis revealed that a general factor and a single-group factor (with high loadings on delusions, hallucinations, apathy, and appetite) underpinned the NPI-Q domains. Significant negative correlations between the Montreal Cognitive Assessment (MoCA) total score and the general and single-group NPI-Q scores were found in all subjects (aMCI + AD combined) and AD, but not in aMCI. Cluster analysis allocated subjects with BPSD (10% of aMCI and 50% of AD participants) into a distinct ‘AD + BPSD’ class.Conclusion:The NPI-Q total score, which is an appropriate index of BPSD, is largely predicted by cognitive deficits. It is plausible that aMCI subjects with severe NPI-Q symptoms (10% of our sample) may have a poorer prognosis and constitute a subgroup of aMCI patients who will likely convert into AD.
Variation in Ecological Scorecards and their Potential for Wider Use: An Irish Case Study
Authors: Gorman Thomas , Morley Terry R , Kindermann Gesche
Published: December 2022

Ecological monitoring is a vital tool to help us assess habitat condition and understand the mechanism(s) for habitat change. Yet many countries struggle to meet their monitoring requirements in part due to the high assessment workload. Rapid ecological assessment methods may have an important role to play in this regard. Following their success on semi-natural grasslands, they are now being developed for multiple agri-associated habitats such as heathlands and peatlands. Whilst grassland scorecards have shown to be accurate compared to traditional ecological monitoring, less is known about the functionality of these scorecards in heterogenous landscapes. In this study, we selected four existing scorecards to test alongside a prototype. We assessed how these different scorecards measured habitat condition on the same heathland sites. We found that the choice of metrics, their score weighting, and the thresholds used for categorical scores cause scorecards to assess the same site with substantial variation (37%). Vegetation metrics were the primary cause of score variation, with vegetation structure and positive indicator species being the leading causes. Our study indicates that while current scorecards may be representative of project specific goals, they may not be suitable for wider monitoring uses in their current form. Ecological scorecards have great potential to drastically increase the extent of monitoring, but caution is needed before adapting existing scorecards beyond the purposes from which they were designed.
Risk factors for subsequent lupus nephritis in patients with juvenile-onset systemic lupus erythematosus: A retrospective cohort study
Authors: Hsu Tzu-Chuan , Yang Yao-Hsu , Wang Li-Chieh , Lee Jyh-Hong , Yu Hsin-Hui , Lin Yu-Tsan , Hu Ya-Chiao , Chiang Bor-Luen
Published: December 2022

Background: Lupus nephritis (LN) is a crucial organ involvement in systemic lupus erythematosus (SLE). Patients with LN have higher morbidity and mortality ratesthan those without. Among all patients with LN, 20–40% haddelayed onset, but the data for patients with juvenile-onset SLE (jSLE), who have a higher percentage of LN than patients with adult-onset SLE (aSLE), were limited. This study aimedto determine the risk factors for subsequent LN in patients with jSLE.
Methods: A retrospective cohort study was conducted between 2008 and 2018 in a single tertiary medical centre. Patients with diagnosed jSLE were reviewed. We investigated those without LN and traced whether they developed LN during the following time. The primary outcome was the development of subsequent LN. Clinicalmanifestations at diagnosis, serial laboratory data, and treatments were reviewed during follow-up periods.
Results: Among the 48 patients with jSLE without initial LN, 20 developed subsequent LN later (Group 1), whereas28 remained free of LN (Group 2). There was no difference in the percentage of initial manifestations except for more discoid rashes in Group2 patients. In the Cox regression model, elevated average anti-double-stranded DNA (dsDNA) antibody, low average serum complements, and high average erythrocyte sedimentation rate (ESR) levels during follow-up were predictors of subsequent LN. After adjusting for these factors in multivariable analyses, only high average anti-dsDNA antibody and high average ESR levels remained predictive of subsequent LN. For every 100 IU/ml increase inanti-dsDNA antibody, the risk for subsequent LN in jSLE increases by 1.29 times (hazard ratio=1.29, 95% confidence interval 1.055–1.573).
Conclusion: Persistently high anti-dsDNA antibody and ESR levels during the follow-up period were risk factors for subsequent LN in patients with jSLE.
Efficiency of mapping epistatic quantitative trait loci
Authors: Viana José Marcelo , Souza Camila
Published: December 2022

Most theoretical studies on epistatic QTL mapping have shown that this procedure is powerful, efficient to control the false positive rate (FPR), and precise to localize QTLs. The objective of this simulation-based study was to show that mapping epistatic QTLs is not an almost perfect process. We simulated 50 samples of 400 F2 plants, genotyped for 975 SNPs distributed in 10 chromosomes of 100 cM. The plants were phenotyped for grain yield, assuming 10 epistatic QTLs and 90 minor genes. Adopting basic procedures of r/qtl package we maximized the power of detection for QTLs (56-74%, on average) but associated with a very high FPR (65%) and a low detection power for the epistatic pairs (7%). Increasing the average detection power for epistatic pairs (14%) highly increased the related FPR. Adopting a procedure to find the best balance between power and FPR, there was a significant decrease in the power of QTL detection (17-31%, on average), associated with a low average detection power for epistatic pairs (8%) and an average FPR of 31% for QTLs and 16% for epistatic pairs. The main reasons for these negative results are a simplified specification of the coefficients of epistatic effects, as theoretically proved, and the effects of minor genes since 2/3 of the FPR for QTLs were due to them. We hope that this study, including the partial derivation of the coefficients of epistatic effects, motivates investigations on how to increase the power of detection for QTLs and epistatic pairs, effectively controlling the FPR.
Optimization of polymyxin B regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: a real-world prospective study
Authors: Tang Tiantian , Li Ying , Xu Ping , Zhong Yanjun , Yang Min , Ma Wanjun , Xiang Daxiong , Zhou Yangang , Zhang Bikui
Published: December 2022

Background
Polymyxin B is the first line therapy for Carbapenem-resistant organism (CRO) nosocomial pneumonia. However, clinical data for its pharmacokinetic/pharmacodynamic (PK/PD) relationship is limited. This study aimed to investigate the relationship between polymyxin B exposure and efficacy for the treatment of CRO pneumonia in critically ill patients, and to optimize the individual dosing regimens.
Methods
Patients treated with polymyxin B for CRO pneumonia were enrolled. Blood samples were assayed using a validated high-performance liquid chromatography-tandem mass spectrometry method. Population PK analysis and monte carlo simulation were performed using Phoenix NLME software. Logistic regression analyses and receiver operating characteristic (ROC) curve were employed to identify the significant predictors and PK/PD indices of polymyxin B efficacy.
Results
A total of 105 patients were included, and the population PK model was developed based on 295 plasma concentrations. AUCss,24h/MIC (AOR = 0.97, 95% CI 0.95–0.99, p = 0.009), daily dose (AOR = 0.98, 95% CI 0.97–0.99, p = 0.028), and combination of inhaled polymyxin B were independent risk factors for polymyxin B efficacy. ROC curve showed that AUCss,24h/MIC is the most predictive PK/PD index and the optimal cut-off point value was 66.9. Model-based simulation suggests that the maintaining daily dose of 75 and 100mg Q12 h could achieve ≥ 90% PTA of this clinical target at MIC values ≤ 0.5 and 1 mg/L, respectively. For patients unable to achieve the target concentration by intravenous administration, adjunctive inhalation of polymyxin B would be beneficial.
Conclusions
For CRO pneumonia, daily dose of 75 and 100 mg Q12h was recommended for clinical efficacy. Inhalation of polymyxin B is beneficial for patients who cannot achieve the target concentration by intravenous administration.
Source apportionment of heavy metal(loid)s in sediments of a typical karst mountain drinking water reservoir and the associated risk assessment based on chemical speciation
Authors: Chen Xue , Wu Pan , Chen Xue , Liu Hongyan , Li Xuexian
Published: December 2022

As important place for water storage and supply, karst reservoirs play a key role in ensuring human well-being, and its water quality safety has attracted much attention. Source apportionment and ecological risks of heavy metal(loid)s in sediments of drinking-water reservoir are of great significance to ensure the safety of water quality and public health, especially in karst mountain areas where water resources are scarce. To expound the accumulation, potential ecological risks and sources of heavy metal(loid)s in a drinking-water reservoir from Northwest Guizhou, China, the surface sediments were collected and analyzed based on the combined use of the geo-accumulation index (Igeo), sequential extraction (BCR), ratios of secondary phase and primary phase (RSP), risk assessment code (RAC), modified potential ecological risk index (MRI), as well as the Positive Matrix Factorization (PMF) methods. Results showed that the concentrations of Cd, As, Pb, Cr, Cu, Ni, and Zn in sediments exceeded the corresponding background values of soils in Guizhou Province. The Igeo indicated that the accumulation of Cd was high, approximately 61.9% of the samples were at moderate and above accumulation levels, followed by Pb, Cu, Ni, and Zn, whereas the As and Cr were at low level. Based on the sum of toxic units (STU), the surface sediments in the reservoir showed a moderate level of toxicity. A large proportion of BCR-extracted acid extractable and reducible fraction was found in Cd (72.5%) and Pb (40.3%), suggesting high bioavailability. Combined RSP, RAC and MRI results showed that Cd was the major pollutants, which had a higher potential risk, while the other elements were at a lower risk level. Source apportionment of heavy metal(loid)s in the drinking-water reservoir indicated that Cd (75.76%) and Zn (23.1%) mainly originated from agricultural activities; As(69.82%), Cr(50.05%), Cu(33.47%), and Ni(31.87%) were associated with domestic sources related to residents' lives; Cu (52.36%), Ni (44.57%), Cr (34.33%), As (26.51%), Pb (24.77%), and Zn (23.80%) were primarily from natural geological sources; and Pb (47.56%), Zn (22.46%) and Cr (13.92%) might be introduced by mixed sources of traffic and domestic. The contribution ratios of the four sources were 18.41%, 36.67%, 29.48% and 15.44%, respectively.
Defining of the Supportive Care Needs of Using Hormone Therapy Patients Have Prostate Cancer and Caregivers
Authors: Tanış Esra Uslu , Uğur Özlem
Published: December 2022

Introduction This study is important in producing effective results in the symptoms of problems faced by prostate cancer patients using hormone therapy and their caregivers. This study defines the support care service needs of those undergoing hormone therapy for prostate cancer and their caregivers.
Methods This is a cross-sectional definitive study. The results of the study were compiled during face-to-face interviews between the dates of February and June 2022. The study involved the participation of 66 prostate cancer patients and 66 caregivers. Later, two of the caregivers declined participation and the study continued with 64 caregivers.
Results The participating patients were defined as 50% over the age of 60. The caregivers were defined as 79.9% being female and 43.8 % being patients’ wives. 36% of the patients had 80-90% performance rates on the Kamofsky scale. The patients had a 9.32% need for sexual support before and after the diagnosis and for those with water retention 46.27% needed supportive care. Of the caregivers, 40.88% needed family support, and 21.25% needed social services support.
Conclusions It has been determined that the difficulties experienced by prostate cancer patients receiving hormone therapy and their caregivers have increased their supportive care needs.
Acute isolation increases reward responsiveness in human adolescents
Authors: Tomova Livia , Towner Emily , Thomas Kirsten , Blakemore Sarah-Jayne
Published: December 2022

Social connection is a basic human need and particularly important during adolescence. How a lack of connection impacts adolescent behaviour is unclear. To address this question, we employed experimental short-term isolation, first, to assess how isolation affects reward seeking and learning in adolescents aged 16-19 years and, second, to investigate whether neural reward sensitivity predicts vulnerability to isolation. Additionally, we assessed whether virtual interactions remediate isolation effects. Isolation caused faster decisions to exert effort for rewards and faster learned reward contingencies, especially from social feedback. These effects were stronger in participants who experienced higher loneliness following isolation. Participants with lower neural reward sensitivity showed stronger effects of isolation. Virtual interactions remediated effects only partially and decreased learning from social feedback. These results demonstrate that in adolescence isolation increases reward responsiveness, a key driver of motivation and decision-making.
Average and extreme heatwaves in Europe at 0.5–2.0°C global warming levels in CMIP6 model simulations
Authors: Ruosteenoja Kimmo , Jylhä Kirsti
Published: December 2022

European heatwaves at the 0.5, 1.0, 1.5 and 2.0°C global warming levels are examined using bias-corrected daily-mean temperature data from 60 simulations performed with 25 global climate models (GCMs). A heatwave event is defined to consist of at least three consecutive days above the 90th percentile of summer daily-mean temperatures and the event is terminated by two days below the threshold temperature.At the 2.0°C global warming level compared with 0.5°C,the multi-GCM mean annual count of heatwave days is projected to be 3--4-fold in northern and more than six-fold in southern Europe. The total annual heatwave extremity index, or the sum of exceedings above the threshold temperature over all the heatwave days, becomes approximatively four-fold in the north and ten-fold in the south. In central Europe, the date of the strongest heatwave of year is delayed by about one week.By concatenating the bias-corrected output data of all the GCM runs, 1200-year samples can be created for all four warming levels, from which the return levels of the strongest heatwaves can be determined very robustly. An intense heatwave occurring once in 10 years at the 0.5°C warming level has an annual probability of about 50% in northern and 80-90% in southern Europe under 2.0°C. Corresponding probabilities for 100-year heatwaves would be nearly 20% in the north and about 60% in the south.Finally, we discuss factors that explain the stronger increase in heatwave duration and extremity in the south than north.
Antibiotic Resistance Clinical Research in Iran: A Scoping Review
Authors: Bonyani Atousa , Mesgarpour Bita , Taheri Forouzan , Nasiri Mohammad Javad , Soleymani Fatemeh , Khorasani Elahe , Kabiri Payam , Hosseinzadeh Maryam
Published: December 2022

Background: In recent years, Anti-Microbial Resistance (AMR) has become a global public health threat. Health system decision-makers need valid and reliable situation analysis to better plan for mitigating this threat. This scoping review investigates the research gaps on AMR publications in Iran and provides an evidential base to support the identification of priority research to better address antibiotic resistance needs in Iran.
Method: A search of four academic databases, including Scopus, ISI web of Science, MEDLINE/ PubMed, EMBASE and IDML was performed in February 2018. The identified studies evaluated the resistance or susceptibility of antibiotics against any bacteria in an Iranian population. Title, abstract, and full-text screening were conducted, and the included studies were accordingly analyzed with respect to the study protocol.
Result: From the 37,769 identified studies, 1,718 studies met all the inclusion criteria. These studies have been evaluated the susceptibility of 131 antibiotics to 82 types of bacteria by conducting 3,509 antibiotic resistances tests. Ofloxacin, ciprofloxacin, and gentamicin had the highest number of studies, samples, and tested bacteria. Regarding the characteristics of the studies, 306 studies had an insufficient explicit definition of study characteristics, 231 studies published their result more than three years after conducting them, and 803 studies (46.7% ) were published in the local journals.
Conclusion: Considering the AMR crisis importance, this scoping review debates the low quality of reporting in AMR-related publications in Iran despite the extensive research.
Changes and Variability in rainfall onset, cessation and length of rainy season in the IGAD region of Eastern Africa
Authors: Omay Paulino Omoj , Muthama Nzioka John , Christopher Oludhe , Kinama Josiah Mwivandi , Artan Guleid , Atheru Zachary Atheru Zachary
Published: December 2022

Rainfall Onset Dates (ROD), Rainfall Cessation Dates (RCD) and Length of rainy Season (LRS) are crucial for Crop production and food security in Eastern Africa yet scantily documented. This paper seeks to investigate the spatial patterns of these parameters. Data used are Climate Hazards Group InfraRed Precipitation with Station data (CHIRPS) and National Oceanic and Atmospheric Administration (NOAA) gridded temperature. Threshold of 0.1mm for rainy day, 20mm over 5 days with at least 3 rain days and dry spell not exceeding 7 days in the next 21 days were used to determine RODs, while Potential Evapotranspiration (PET) and Water Balance (WB) criteria were computed to determine RCDs then differences between ROD and RCD were used in calculating LRS. The results showed early rainfall cessation over more than 30 counties in Kenya lead to shortened rainy season by 10–20 days during MAM season. Similarly, 20–40 days early onset dates are observed in most counties in upper Nile, Unity and Jonglei states in South Sudan, while 20–40 days delayed rainfall onset was observed in Khartoum and southern parts of Nile state western Darfur, eastern and Aljazeera states in Sudan, most parts of Ethiopia and Eritrea districts during JJA season. Highlands of western and Nyanza region in Kenya, most parts of Uganda observed rainfall onset by March and no sign of cessation before November. Early cessation over northern Uganda districts was behind shortened LRS, furthermore, the early RODs over western and southwestern Uganda districts increased LRS. Prolonged dry conditions over northern Sudan, southeastern parts of South Sudan, northern Kenya, central Somalia, northern Darfour, Kordofan and northern parts of Sudan exacerbated by significant delayed onset and early cessation of rainfall. These findings are important for rain-fed agricultural planning and food security in the IGAD region of Eastern Africa.
Effects of Vitamin E and D on the Stiffness of MCF-7
Authors: Khameneh Armin Jarahi , Heydarian Ashkan , Babaei Nasibeh , Hannani Negin , Milani Dornaz , Sahbafar Hossein
Published: December 2022

Background
Several investigations have demonstrated that vitamins can be used to treat or prevent cancer by altering actin filaments, inhibiting cell migration and cancer cell proliferation. Vitamins D and E are fat-soluble. This research aims to determine the short-term impact of vitamin D and E on the mechanical characteristics of breast cancer cells before comparing them with normal breast cells.
Method
Atomic force microscopy (AFM) was used to examine the deformation of MCF-10 normal breast cells, MCF-7 breast cancer cells, and MCF-7 breast cancer cells treated with 0.03 µM vitamin D and 16 µM vitamin E solution. Young's modulus was calculated employing the Hertz model to determine cell stiffness.
Results
The Young's modulus of vitamin D-treated cancer cells (585.8 Pa) was substantially similar to that of normal cells (455.6 Pa). Nevertheless, vitamin E treatment had no effect on Young's modulus of cancer cells, which remained remarkably similar to that of untreated cancer cells (216.6 and 203.4 Pa, respectively).
Conclusion
Despite vitamin E, vitamin D enhances the stiffness of tumor cells and puts their mechanical characteristics similar to normal cells by interfering with actin filaments and cell skeletons, which may inhibit tumor cell migration. According to these findings, Vitamin D appears to be an effective drug for cancer treatment.
Positivity rates of thyroid-associated autoantibodies and thyroid morphological changes in subjects with chronic thyroiditis
Authors: Iwamoto Yuichiro , Kimura Tomohiko , Itoh Takashi , Mori Shigehito , Sasaki Taku , Sugisaki Toshitomo , Nakao Erina , Ohnishi Mana , Kusano Takashi , Takenouchi Haruka , Iwamoto Hideyuki , Sanada Junpei , Fushimi Yoshiro , Katakura Yukino , Shimoda Masashi , Nakanishi Shuhei , Mune Tomoatsu , Kaku Kohei , Kaneto Hideaki
Published: December 2022

Background
Most primary hypothyroidism in adults is caused by chronic thyroiditis. Autoantibodies such as anti-thyroglobulin antibody (TgAb) and anti-thyroid peroxidase antibody (TPOAb) are involved in the pathogenesis of chronic thyroiditis. On the other hand, there have been reports of seronegative chronic thyroiditis, which can make the clinical diagnosis difficult clinically. This study aimed to determine the positivity rate of thyroid-related autoantibodies in patients with chronic thyroiditis and to evaluate the differences in clinical findings in seropositive and seronegative chronic thyroiditis.
Method
In 804 patients with hypothyroidism who attended Kawasaki Medical School Hospital between January 1, 2010 and December 31, 2021, 360 patients were diagnosed with chronic thyroiditis by thyroid antibody testing and ultrasonography. Their thyroid antibody positivity rates and clinical findings were compared.
Results
Among the patients with chronic thyroiditis, 27.5% were participants with seronegative chronic thyroiditis. The positive rate of each antibody was 68.3% for TgAb and 52.2% for TPOAb. The participants with seropositive chronic thyroiditis had significantly more thyroid gland enlargement on thyroid ultrasound examination (p < 0.05). Thyroid-stimulating hormone was significantly higher in participants with seropositive compared to seronegative chronic thyroiditis. Levothyroxine dosage did not differ between the both groups.
Conclusion
The present study reveals a positive rate of thyroid-related autoantibodies at the time of diagnosis of chronic thyroiditis. The data of this study also revealed differences in the clinical presentation of seropositive and seronegative chronic thyroiditis.
Classification of odorant substances that trigger migraine attacks: a cross-sectional study
Authors: Imai Noboru , Osanai Ayako , Moriya Asami , Katsuki Masahito , Kitamura Eiji
Published: December 2022

Background
Migraine is a common primary headache disorder that can be induced by various factors such as stress, hormones in women, fasting, weather, and sleep disturbance. Odorant substances are also common triggers of migraine attacks. We aimed to categorize odorant substances that trigger migraine and explore their relationships with clinical characteristics.
Methods
A total of 101 migraineurs were included in our study. A questionnaire was used to determine the types of odorant substances that triggered migraine attacks. We performed factor analysis to explore the common factors of the odorant substances and the relationship between these factors and the clinical characteristics.
Results
The factor analysis estimated six common factors. We defined factor 1 as fetid odor, factor 2 as cooking products, factor 3 as oil derivatives and others, factor 4 as shampoo and conditioner, factor 5 as hair styling preparation and cleaning products, and factor 6 as perfumes, insecticides, and rose. Factor 5 also included hair styling preparation, laundry detergent, and fabric softener, usually added with floral fragrances. It was more likely to trigger migraine attacks in chronic than in episodic migraine patients (p = 0.037).
Conclusion
Our study showed that odorant substances that trigger migraine attacks could be categorized into six groups and suggested that some chemicals were more likely to trigger migraine attacks in patients with chronic migraine than in those with episodic migraine.