bluuebunny/crossref_metadata_2025_split huggingface dataset:
Farmability and pharmability: Transforming the drug market to a health-and human rights-centred approach from self-cultivation to safe supply of controlled substances
Authors: Steinmetz Fabian Pitter , Kohek Maja 
Published: May 2022

Background The supply chains addressing the global demand for major recreational drugs are hardly addressed due to international contracts, particularly the UN Single Convention on Narcotic Drugs. Currently applied regulatory changes have several disadvantages ranging from political tensions to the neglect of ecological aspects. The aim of this study is to show some implications associated with a transformation of the recreational drug market that is focused on self-supply of different categories of drugs. The concepts of "farmability", the feasibility to cultivate relevant plants and fungi, and "pharmability", the feasibility to refine materials to drugs by chemical synthesis, purification etc., are addressed. Methods 68 drug experts were invited to fill out an online survey on the feasibility of self-supply of different categories of drugs. The online survey was a five-point Likert scale and had seven questions. Results 26 experts (38.2%) responded to the online questionnaire. Cannabinoids were considered easy to cultivate/manufacture, depressants and psychedelics were ranked with moderate difficulty, opioids and stimulants were regarded as difficult to cultivate/manufacture, and empathogens/entactogens and dissociatives were ranked very difficult. The study found that some controlled substances, in particular cannabis, could be decriminalised without the need for a commercial market. However, some drug categories, such as dissociatives and empathogens/entactogens, would require the establishment of professional manufacturers. Psychedelics and depressants are ranked in between. Conclusion Different drugs are associated with different cultivation and/or manufacturing steps with contrasting difficulty levels. Those differences are likely to shape use prevalence to more accessible and safer drug markets which also decrease the involvement of organised crime groups. Hence, when decriminalising the possession of drugs for personal use, it is therefore recommended to allow also for personal cultivation or cultivation within social clubs. This is particularly relevant for drugs with moderate to high farmability but also if pharmability is sufficiently high.
Overlapping and unique substrate specificities of ST3GAL1 and 2 during hematopoietic and megakaryocytic differentiation
Authors: Zhang Nanyan , Lin Siying , Cui Weiguo , Newman Peter J. 
Published: May 2022

Abstract
Although the sialyltransferases ST3GAL1 and ST3GAL2 are known to transfer sialic acid to the galactose residue of type III disaccharides (Galβ1,3GalNAc) in vitro, sialylation of O-linked glycosylated proteins in living cells has been largely attributed to ST3GAL1. To examine the role of ST3GAL2 in O-sialylation, we examined its expression during differentiation of human-induced pluripotent stem cells (iPSCs) into hematopoietic progenitor cells (HPCs) and megakaryocytes (MKs). ST3GAL1 and ST3GAL2 each became highly expressed during the differentiation of iPSCs to HPCs but decreased markedly in their expression upon differentiation into MKs, suggesting coordination of expression during megakaryopoiesis. To further delineate their role in these processes, we generated ST3GAL1-, ST3GAL2-, and doubly deficient human iPSC lines. Binding of the peanut agglutinin lectin, which reports the presence of unsialylated Galβ1,3GalNAc glycan chains, was strongly increased in HPCs and MKs derived from double-knockout iPSCs and remained moderately increased in cells lacking either one of these sialyltransferases, demonstrating that both can serve as functional cellular O-glycan sialyltransferases. Interestingly, the HPC markers CD34 and CD43, as well as MK membrane glycoprotein (GP) GPIbα, were identified as major GP substrates for ST3GAL1 and ST3GAL2. In contrast, O-sialylation of GPIIb relied predominantly on the expression of ST3GAL2. Finally, although disruption of ST3GAL1 and ST3GAL2 had little impact on MK production, their absence resulted in dramatically impaired MK proplatelet formation. Taken together, these data establish heretofore unknown physiological roles for ST3GAL1 and ST3GAL2 in O-linked glycan sialylation in hemato- and megakaryocytopoiesis.
Predicting circRNA-drug sensitivity associations via graph attention auto-encoder
Authors: Deng Lei , Liu Zixuan , Qian Yurong , Zhang Jingpu 
Published: May 2022

Abstract
Background
Circular RNAs (circRNAs) play essential roles in cancer development and therapy resistance. Many studies have shown that circRNA is closely related to human health. The expression of circRNAs also affects the sensitivity of cells to drugs, thereby significantly affecting the efficacy of drugs. However, traditional biological experiments are time-consuming and expensive to validate drug-related circRNAs. Therefore, it is an important and urgent task to develop an effective computational method for predicting unknown circRNA-drug associations.

Results
In this work, we propose a computational framework (GATECDA) based on graph attention auto-encoder to predict circRNA-drug sensitivity associations. In GATECDA, we leverage multiple databases, containing the sequences of host genes of circRNAs, the structure of drugs, and circRNA-drug sensitivity associations. Based on the data, GATECDA employs Graph attention auto-encoder (GATE) to extract the low-dimensional representation of circRNA/drug, effectively retaining critical information in sparse high-dimensional features and realizing the effective fusion of nodes’ neighborhood information. Experimental results indicate that GATECDA achieves an average AUC of 89.18% under 10-fold cross-validation. Case studies further show the excellent performance of GATECDA.

Conclusions
Many experimental results and case studies show that our proposed GATECDA method can effectively predict the circRNA-drug sensitivity associations.
Marine protected areas do not buffer corals from bleaching under global warming
Authors: Johnson Jack V. , Dick Jaimie T. A. , Pincheira-Donoso Daniel 
Published: May 2022

Abstract
Background
The rising temperature of the oceans has been identified as the primary driver of mass coral reef declines via coral bleaching (expulsion of photosynthetic endosymbionts). Marine protected areas (MPAs) have been implemented throughout the oceans with the aim of mitigating the impact of local stressors, enhancing fish biomass, and sustaining biodiversity overall. In coral reef regions specifically, protection from local stressors and the enhanced ecosystem function contributed by MPAs are expected to increase coral resistance to global-scale stressors such as marine heatwaves. However, MPAs still suffer from limitations in design, or fail to be adequately enforced, potentially reducing their intended efficacy. Here, we address the hypothesis that the local-scale benefits resulting from MPAs moderate coral bleaching under global warming related stress.

Results
Bayesian analyses reveal that bleaching is expected to occur in both larger and older MPAs when corals are under thermal stress from marine heatwaves (quantified as Degree Heating Weeks, DHW), but this is partially moderated in comparison to the effects of DHW alone. Further analyses failed to identify differences in bleaching prevalence in MPAs relative to non-MPAs for coral reefs experiencing different levels of thermal stress. Finally, no difference in temperatures where bleaching occurs between MPA and non-MPA sites was found.

Conclusions
Our findings suggest that bleaching is likely to occur under global warming regardless of protected status. Thus, while protected areas have key roles for maintaining ecosystem function and local livelihoods, combatting the source of global warming remains the best way to prevent the decline of coral reefs via coral bleaching.
Genome-wide association study reveals the genetic architecture for calcium accumulation in grains of hexaploid wheat (Triticum aestivum L.)
Authors: Shi Xia , Zhou Zhengfu , Li Wenxu , Qin Maomao , Yang Pan , Hou Jinna , Huang Fangfang , Lei Zhensheng , Wu Zhengqing , Wang Jiansheng 
Published: May 2022

Abstract
Background
Hexaploid wheat (Triticum aestivum L.) is a leading cereal crop worldwide. Understanding the mechanism of calcium (Ca) accumulation in wheat is important to reduce the risk of human micronutrient deficiencies. However, the mechanisms of Ca accumulation in wheat grain are only partly understood.

Results
Here, a genome-wide association study (GWAS) was performed to dissect the genetic basis of Ca accumulation in wheat grain using an association population consisting of 207 varieties, with phenotypic data from three locations. In total, 11 non-redundant genetic loci associated with Ca concentration were identified and they explained, on average, 9.61–26.93% of the phenotypic variation. Cultivars containing more superior alleles had increased grain Ca concentrations. Notably, four non-redundant loci were mutually verified by different statistical models in at least two environments, indicating their stability across different environments. Four putative candidate genes linked to Ca accumulation were revealed from the stable genetic loci. Among them, two genes, associated with the stable genetic loci on chromosomes 4A (AX-108912427) and 3B (AX-110922471), encode the subunits of V-type Proton ATPase (TraesCS4A02G428900 and TraesCS3B02G241000), which annotated as the typical generators of a proton gradient that might be involved in Ca homeostasis in wheat grain.

Conclusion
To identify genetic loci associated with Ca accumulation, we conducted GWAS on Ca concentrations and detected 11 genetic loci; whereas four genetic loci were stable across different environments. A genetic loci hot spot exists at the end of chromosome 4A and associated with the putative candidate gene TraesCS4A02G428900. The candidate gene TraesCS4A02G428900 encodes V-type proton ATPase subunit e and highly expressed in wheat grains, and it possibly involved in Ca accumulation. This study increases our understanding of the genetic architecture of Ca accumulation in wheat grains, which is potentially helpful for wheat Ca biofortification pyramid breeding.
Efficacy of using tidal volume challenge to improve the reliability of pulse pressure variation reduced in low tidal volume ventilated critically ill patients with decreased respiratory system compliance
Authors: Xu Yujun , Guo Jun , Wu Qin , Chen Junjun 
Published: May 2022

Abstract
Background
The prediction accuracy of pulse pressure variation (PPV) for fluid responsiveness was proposed to be unreliable in low tidal volume (Vt) ventilation. It was suggested that changes in PPV obtained by transiently increasing Vt to 8 ml/kg accurately predicted fluid responsiveness even in subjects receiving low Vt. We assessed whether the changes in PPV induced by a Vt challenge predicted fluid responsiveness in our critically ill subjects ventilated with low Vt 6 ml/kg.

Methods
This study is a prospective single-center study. PPV and other parameters were measured at a Vt of 6 mL/kg, 8 mL/kg, and after volume expansion. The prediction accuracy of PPV and other parameters for fluid responsiveness before and after tidal volume challenge was also analyzed using receiver operating characteristic (ROC) curves.

Results
Thirty-one of the 76 subjects enrolled in the study were responders (41%). Respiratory system compliance of all subjects decreased significantly (26 ± 4.3). The PPV values were significantly higher in the responder group than the non-responder group before (8.8 ± 2.7 vs 6.8 ± 3.1) or after (13.0 ± 1.7 vs 8.5 ± 3.0) Vt challenge. In the receiver operating characteristic curve (ROC) analysis, PPV6 showed unsatisfactory predictive capability with an area under the curve (AUC) of 0.69 (95%CI, 0.57–0.79, p = 0.002) at a Vt of 6 mL/kg. PPV8 andΔPPV6–8 showed good predictive capability with an AUC of 0.90 (95% CI, 0.81–0.96, p < 0.001) and 0.90 (95% CI, 0.80–0.95, P < 0.001) respectively. The corresponding cutoff values were 11% for PPV8 and 2% for ΔPPV6–8.

Conclusions
PPV shows a poor operative performance as a predictor of fluid responsiveness in critically ill subjects ventilated with a tidal volume of 6 mL/ kg. Vt challenge could improve the predictive accuracy of PPV to a good but not excellent extent when respiratory system compliance decreased significantly.
Gitelman syndrome with normocalciuria – a case report
Authors: Flisiński Mariusz , Skalska Ewa , Mączyńska Barbara , Butt-Hussaim Natalia , Sobczyńska-Tomaszewska Agnieszka , Haus Olga , Manitius Jacek 
Published: May 2022

Abstract
Background
Gitelman Syndrome (GS) is a hereditary tubulopathy associated with a biallelic inactivating mutations of the SLC12A3 gene encoding the thiazide-sensitive sodium-chloride cotransporter (NCCT). The typical clinical manifestation is a hypokalemic metabolic alkalosis with significant hypomagnesemia, and low urinary calcium excretion. Hypocalciuria is widely believed to be a hallmark of GS that distinguishes it from Barter’s syndrome, presenting as hypercalciuria. The pathomechanism of hypocalciuria in GS is not fully elucidated. Up to date, a clinical course of GS with normocalciuria has been reported only in men, while women have a milder course of the disease with typical hypocalciuria, which is believed as the result of sex hormone. Additionally, there is a growing evidence that calcium channels of the distal nephron could be regulated by a variety of hormones, including aldosterone (Aldo).

Case presentation
We present the case of a 28-year-old Caucasian woman with asymptomatic, chronic hypokalemia, hypomagnesemia, hypochloremic alkalosis and normal urinary calcium excretion. A high renin levels with normal concentration of Aldo in serum have also been found. The values of blood pressure were low. Based on genetic studies, two heterozygous mutations in the trans position were confirmed: c.2186G>T (p.Gly729Val) and c.1247G>C (p.Cys416Ser) in the SLC12A3 gene, which ultimately confirmed the diagnosis of GS.

Conclusions
We report here the first case of genetically confirmed GS manifested as normocalciuria in a Caucasian woman. Thus, our result does not confirm a role of sex hormones on the level of calciuria. Based on the results of normal Aldo concentration despite high renin level in our patient, we hypothesized that Aldo may be connecting with the level of urinary calcium excretion in patients with the GS.
Application of machine learning methods for predicting infant mortality in Rwanda: analysis of Rwanda demographic health survey 2014–15 dataset
Authors: Mfateneza Emmanuel , Rutayisire Pierre Claver , Biracyaza Emmanuel , Musafiri Sanctus , Mpabuka Willy Gasafari 
Published: May 2022

Abstract
Background
Extensive research on infant mortality (IM) exists in developing countries; however, most of the methods applied thus far relied on conventional regression analyses with limited prediction capability. Advanced of Machine Learning (AML) methods provide accurate prediction of IM; however, there is no study conducted using ML methods in Rwanda. This study, therefore, applied Machine Learning Methods for predicting infant mortality in Rwanda.

Methods
A cross-sectional study design was conducted using the 2014–15 Rwanda Demographic and Health Survey. Python software version 3.8 was employed to test and apply ML methods through Random Forest (RF), Decision Tree, Support Vector Machine and Logistic regression. STATA version 13 was used for analysing conventional methods. Evaluation metrics methods specifically confusion matrix, accuracy, precision, recall, F1 score, and Area under the Receiver Operating Characteristics (AUROC) were used to evaluate the performance of predictive models.

Results
Ability of prediction was between 68.6% and 61.5% for AML. We preferred with the RF model (61.5%) presenting the best performance. The RF model was the best predictive model of IM with accuracy (84.3%), recall (91.3%), precision (80.3%), F1 score (85.5%), and AUROC (84.2%); followed by decision tree model with model accuracy (83%), recall (91%), precision (79%), F1 score (84.67%) and AUROC(82.9%), followed by support vector machine with model accuracy (68.6%), recall (74.9%), precision(67%), F1 score (70.73%) and AUROC (68.6%) and last was a logistic regression with the low accuracy of prediction (61.5%), recall (61.1%), precision (62.2%), F1 score (61.6%) and AUROC (61.5%) compared to other predictive models. Our predictive models showed that marital status, children ever born, birth order and wealth index are the 4 top predictors of IM.

Conclusions
In developing a predictive model, ML methods are used to classify certain hidden information that could not be detected by traditional statistical methods. Random Forest was classified as the best classifier to be used for the predictive models of IM.
An analysis of age-standardized suicide rates in Muslim-majority countries in 2000-2019
Authors: Lew Bob , Lester David , Kõlves Kairi , Yip Paul S. F. , Chen Ying-Yeh , Chen Won Sun , Hasan M. Tasdik , Koenig Harold G. , Wang Zhi Zhong , Fariduddin Muhamad Nur , Zeyrek-Rios Emek Yuce , Chan Caryn Mei Hsien , Mustapha Feisul , Fitriana Mimi , Dolo Housseini , Gönültaş Burak M. , Dadfar Mahboubeh , Davoudi Mojtaba , Abdel-Khalek Ahmed M. , Chan Lai Fong , Siau Ching Sin , Ibrahim Norhayati 
Published: May 2022

Abstract
Background
This study examines the 20-year trend of suicide in 46 Muslim-majority countries throughout the world and compares their suicide rates and trends with the global average. Ecological-level associations between the proportion of the Muslim population, the age-standardized suicide rates, male-to-female suicide rate ratio, and the Human Development Index (HDI) in 2019 were examined.

Methods
Age-standardized suicide rates were extracted from the WHO Global Health Estimates database for the period between 2000 and 2019. The rates in each country were compared with the age-standardized global average during the past 20 years. The countries were further grouped according to their regions/sub-regions to calculate the regional and sub-regional weighted age-standardized suicide rates involving Muslim-majority countries. Correlation analyses were conducted between the proportion of Muslims, age-standardized suicide rate, male: female suicide rate ratio, and the HDI in all countries. Joinpoint regression was used to analyze the age-standardized suicide rates in 2000-2019.

Results
The 46 countries retained for analysis included an estimated 1.39 billion Muslims from a total worldwide Muslim population of 1.57 billion. Of these countries, eleven (23.9%) had an age-standardized suicide rate above the global average in 2019. In terms of regional/sub-regional suicide rates, Muslim-majority countries in the Sub-Saharan region recorded the highest weighted average age-standardized suicide rate of 10.02/100,000 population, and Southeastern Asia recorded the lowest rate (2.58/100,000 population). There were significant correlations between the Muslim population proportion and male-to-female rate ratios (r=-0.324, p=0.028), HDI index and age-standardized suicide rates (r=-0.506, p<0.001), and HDI index and male-to-female rate ratios (r=0.503, p<0.001) in 2019. Joinpoint analysis revealed that seven Muslim-majority countries (15.2%) recorded an increase in the average annual percentage change regarding age-standardized suicide rates during 2000-2019.

Conclusions
Most Muslim-majority countries had lower age-standardized suicide rates than the global average, which might reflect religious belief and practice or due to Muslim laws in their judicial and social structure which may lead to underreporting. This finding needs further in-depth country and region-specific study with regard to its implication for public policy.
United for health to improve urban food environments across five underserved communities: a cross-sector coalition approach
Authors: Payán Denise D. , Lewis LaVonna B. , Illum Jacqueline , Hawkins Breanna , Sloane David C. 
Published: May 2022

Abstract
Background
Cross-sector coalitions can be a powerful vehicle to promote adoption and implementation of evidence-based programs and policies across diverse racial/ethnic communities with a high chronic disease burden. Few studies have examined coalition composition, function, or capacity to promote learning among members.

Methods
We used a mixed methods approach to examine the United for Health coalition’s implementation of multiple food environment interventions across five low-income communities of color in Los Angeles, California (USA). At the coalition-level, key measures included the collaborative environment, membership characteristics, process and structure, communication, resources, strengths, challenges/barriers, and community impact. At the organizational- and individual-levels, we collected data on participation, leadership development, intraorganizational change, perceived benefits, and learning outcomes.

Findings
Overall, the United for Health coalition produced five community gardens, three pop-up produce markets, and one farmers’ market; members also expanded Electronic Benefits Transfer (EBT) access at three existing farmers’ markets. Findings indicate early coalition strengths included having a mutual purpose, which was maintained throughout the study period. Coalition participation and engagement was consistently high, while coalition and inter-organizational communication improved over time. Strengths were membership diversity and the availability of learning opportunities. Benefits included leadership development and strategic alignment across organizations. Members demonstrated an increased awareness of the importance of culturally adapted interventions and knowledge of community health planning topics. Key implementation challenges were a lack of resources and social context barriers.

Conclusions
Examining coalition function and maturation in a real-world context reveals important lessons for scholars and practitioners committed to addressing nutrition-related health disparities in marginalized and historically underserved communities. Future work should investigate the sustainability of externally funded cross-sector coalitions after funding ceases.