bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interventions for the management of Pain and Sedation in Newborns undergoing Therapeutic hypothermia for hypoxic-ischemic encephalopathy (IPSNUT): protocol of a systematic review
Authors: Bäcke Pyrola , Bruschettini Matteo , Blomqvist Ylva Thernström , Olsson Emma 
Published: May 2022

Abstract
Background
Clinical research has shown that therapeutic hypothermia after neonatal hypoxic-ischemic injury improves survival without disability. There is no consensus regarding pain relief or sedation during therapeutic hypothermia in newborns; however, therapeutic hypothermia seems to be associated with pain and stress, and adequate analgesia and sedation are central to maximize the effect of therapeutic hypothermia. Pain needs to be adequately managed in all patients, especially the newborn infant due to the potential short- and long-term negative effects of inadequately treated pain in this population.

Methods
We will perform a systematic review of pharmacological and non-pharmacological interventions for the management of pain and sedation in newborn infants undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy. We will include randomized, quasi-randomized controlled trials and observational studies. The use of pharmacological or non-pharmacological interventions will be compared to other pharmacological and or non-pharmacological interventions or no intervention/placebo. The primary outcomes for this review will be analgesia and sedation assessed with validated pain scales, circulatory instability, mortality to discharge, and moderate-to-severe neurodevelopmental disability. We will search the following databases: CINAHL, ClinicalTrials.gov, Cochrane Library, Embase, PubMed, Scopus, and Web of Science. Two independent researchers will screen the records for inclusion, extract data using a data extraction form, and assess the risk of bias in the included trials.

Discussion
The result of this review will summarize the knowledge regarding the management of pain and sedation in infants treated with therapeutic hypothermia and potentially provide clinicians with guidance on the effective and safe methods.

Systematic review registration
PROSPERO CRD42020205755
Optimal control of stochastic singular affine systems with Markovian jumps
Authors: Wang Xin , Wang Lisha , Liu Yuxiang 
Published: May 2022

AbstractWe consider an optimal control problem for a class of stochastic singular affine systems with Markovian jumps. We establish the existence and uniqueness of the solution to stochastic singular affine systems with Markovian jumps for the first time. Via square completion technique and the generalized Itô’s formula, we derive new kinds of generalized differential Riccati equations (GDREs) and generalized backward differential equations (GBDEs), which give sufficient conditions for the well-posedness of the optimal control problem, and present an explicit representation of optimal control. Also, we discuss the solvability of the GDREs in two cases. As an application, we present a leader-follower differential game to demonstrate the practicability of our results.
An uncertain production-inventory problem with deteriorating items
Authors: Shen Jiayu , Jin Yueqiang , Liu Bing , Lu Ziqiang , Chen Xin 
Published: May 2022

AbstractThe uncertain production-inventory problem with deteriorating items is investigated and an optimal control model is developed in the present paper. The uncertain production-inventory problem is perturbed by an uncertain canonical process. Based on uncertainty theory, an optimistic-value optimal-based control model is established. The present study aims to find the optimistic value of revenue at a certain confidence level. The uncertainty theory is used to obtain the equation of optimality. Using the Hamilton–Jacobi–Bellman principle, a nonlinear partial differential equation that has to be satisfied by a value function is obtained. Assuming a specific form of the solution, backsubstituting the partial differential equation to find functions of time is conducted, and the functions are then used to solve the partial differential equation. Numerical experiments with different demand functions are used to assess the feasibility of this model and this method.
Factors affecting intention to screen after being informed of benefits and harms of breast cancer screening: a study in 5 European countries in 2021
Authors: Ritchie David , Van Hal Guido , Van den Broucke Stephan 
Published: May 2022

AbstractBackgroundParticipation in mammography screening comes with harms alongside benefits. Information about screening provided to women should convey this information yet concerns persist about its effect on participation. This study addressed factors that may influence the intention to screen once a woman has been informed about benefits and harms of participation.MethodsA cross-sectional survey of women from five countries (Belgium, France, Italy, Spain, and the United Kingdom) was performed in January 2021. The survey contained a statement regarding the benefits and harms of mammography screening along with items to measure cognitive variables from the theory of planned behaviour and health belief model and the 6-item version of the European Health Literacy Survey Questionnaire (HLS-EU-Q6). Logistic regression and mediation analysis were performed to investigate the effect of cognitive and sociodemographic variables.ResultsA total of 1180 participants responded to the survey. 19.5% of participants (n = 230) were able to correctly identify that mammography screening carries both benefits and harms. 56.9% of participants (n = 672) responded that they would be more likely to participate in screening in the future after being informed about the benefits and harms of mammography screening. Perceived behavioural control and social norms demonstrated were significant in predicting intention, whereas, the effect of health literacy was limited.ConclusionsInforming women about the presence of benefits and harms of in mammography screening participation did not negatively impact upon intention to be screened. Information should also address perception on implementation factors alongside messages on benefits and harms. Overall, screening programme managers should not be discouraged by the assumption of decreased participation through increasing efforts to address the lack of knowledge on benefits and harms.
Fungi associated with the potato taste defect in coffee beans from Rwanda
Authors: Hale Amanda R. , Ruegger Paul M. , Rolshausen Philippe , Borneman James , Yang Jiue-in 
Published: May 2022

Abstract
Background
Potato taste defect (PTD) of coffee is characterized by a raw potato like smell that leads to a lower quality taste in the brewed coffee, and harms the commercial value of some East African coffees. Although several causes for PTD have been proposed, none of them have been confirmed. Recently, high throughput sequencing techniques and bioinformatic analysis have shown great potential for identifying putative causal agents of plant diseases. Toward the goal of determining the cause of PTD, we examined raw coffee beans from Rwanda exhibiting varying PTD scores using an Illumina-based sequence analysis of the fungal rRNA ITS region.

Results
Six fungal amplicon sequence variants (ASVs) with high relative abundances correlated with coffee taste scores. Four of these ASVs exhibited negative correlations – Aspergillus versicolor, Penicillium cinnamopurpureum, Talaromyces radicus, and Thermomyces lanuginosus – indicating that they might be causing PTD. Two of these fungi exhibited positive correlations – Kazachstania humilis and Clavispora lusitaniae – indicating that they might be inhibiting organisms that cause PTD.

Conclusions
This study addressed PTD causality from a new angle by examining fungi with high throughput sequencing. To our knowledge, this is the first study characterizing fungi associated with PTD, providing candidates for both causality and biocontrol.
Issues related to velocity structure estimation in small coastal sedimentary plains: case of Tottori plain facing the Sea of Japan
Authors: Kagawa Takao , Noguchi Tatsuya 
Published: May 2022

AbstractIssues of predominant period of ground motion and derived underground velocity structure model are investigated in the coastal plains affected by the shallow soft sedimentary layer after the last ice age. It is found that two predominant periods due to the shallow soft layer and deeper drastic sedimentary boundaries are close in a small plain such as the Tottori plain, Japan as an example. This study analyzes the underground velocity structure derived from EHVSR (H/V spectrum ratio of earthquake ground motions) with the diffuse field theory. It is considered that the interaction of close predominant periods due to the different layer boundaries with high contrast may amplify the seismic ground motion in the period range that affects building structures in small plains in coastal area.
Graphical Abstract
Trialling a microbiome-targeted dietary intervention in children with ADHD—the rationale and a non-randomised feasibility study
Authors: Lawrence Kate , Myrissa Kyriaki , Toribio-Mateas Miguel , Minini Lori , Gregory Alice M. 
Published: May 2022

Abstract
Background
Dietary interventions have been previously explored in children with ADHD. Elimination diets and supplementation can produce beneficial behaviour changes, but little is known about the mechanisms mediating change. We propose that these interventions may work, in part, by causing changes in the gut microbiota. A microbiome-targeted dietary intervention was developed, and its feasibility assessed.

Methods
A non-randomised feasibility study was conducted on nine non-medicated children with ADHD, aged 8–13 years (mean 10.39 years), using a prospective one-group pre-test/post-test design. Participants were recruited from ADHD support groups in London and took part in the 6-week microbiome-targeted dietary intervention, which was specifically designed to impact the composition of gut bacteria. Children were assessed pre- and post-intervention on measures of ADHD symptomatology, cognition, sleep, gut function and stool-sample microbiome analysis. The primary aim was to assess the study completion rate, with secondary aims assessing adherence, adverse events (aiming for no severe and minimal), acceptability and suitability of outcome measures.

Results
Recruitment proved to be challenging and despite targeting 230 participants directly through support groups, and many more through social media, nine families (of the planned 10) signed up for the trial. The completion rate for the study was excellent at 100%. Exploration of secondary aims revealed that (1) adherence to each aspect of the dietary protocol was very good; (2) two mild adverse events were reported; (3) parents rated the treatment as having good acceptability; (4) data collection and outcome measures were broadly feasible for use in an RCT with a few suggestions recommended; (5) descriptive data for outcome measures is presented and suggests that further exploration of gut microbiota, ADHD symptoms and sleep would be helpful in future research.

Conclusions
This study provides preliminary evidence for the feasibility of a microbiome-targeted dietary intervention in children with ADHD. Recruitment was challenging, but the diet itself was well-tolerated and adherence was very good. Families wishing to trial this diet may find it an acceptable intervention. However, recruitment, even for this small pilot study, was challenging. Because of the difficulty experienced recruiting participants, future randomised controlled trials may wish to adopt a simpler dietary approach which requires less parental time and engagement, in order to recruit the number of participants required to make meaningful statistical interpretations of efficacy.

Trial registration
ClinicalTrials.gov Identifier: NCT03737877. Registered 13 November 2018—retrospectively registered, within 2 days of the first participant being recruited.
Two new species of Dugesia (Platyhelminthes, Tricladida, Dugesiidae) from the subtropical monsoon region in Southern China, with a discussion on reproductive modalities
Authors: Chen Guang-wen , Wang Lei , Wu Fan , Sun Xiao-juan , Dong Zi-mei , Sluys Ronald , Yu Fei , Yu-wen Yan-qing , Liu De-zeng 
Published: May 2022

Abstract
Background
Freshwater planarians of the genus Dugesia (Platyhelminthes, Tricladida, Dugesiidae) are distributed in a major part of the Old World and Australia, although until recently only very few species were known from China.

Results
Two new species of Dugesia from Southern China are described on the basis of an integrative taxonomic approach. BI and ML phylogenetic trees based on the independent genes and on the concatenated dataset had similar topologies, only differing in some nodes that were weakly supported. Phylogenetic trees based on the concatenated dataset revealed that D. adunca Chen & Sluys, sp. nov. and D. tumida Chen & Sluys, sp. nov. are not closely related and belong to different clades. The two new species occupy separate long branches with high support values and, thus, are well-differentiated from their congeners. Separate species status of D. adunca and D. tumida is supported also by the genetic distances between the species included in our analysis, albeit that COI distances varied greatly among species. Dugesia adunca from Guangxi Province is characterized by the following features: living mature animals rather small; asymmetrical openings of the oviducts into the bursal canal; penis papilla with shape of an aquiline bill, albeit with a blunt tip; asymmetrical penis papilla, with a large antero-dorsal lip and a much smaller ventro-posterior lip; very large seminal vesicle, provided with trabeculae; small diaphragm; mixoploid karyotype with diploid complements of 2n = 2x = 16 and triploid complements of 2n = 3x = 24, with all chromosomes being metacentric. Dugesia tumida from Guangdong Province is characterized by a penis papilla provided with a large, symmetrical penial valve from the middle of which arises the small, distal section of the papilla; a duct intercalated between the seminal vesicle and the small diaphragm; ventrally displaced ejaculatory duct curving upwards before opening to the exterior; penis papilla highly asymmetrical, having a slim and long ventral portion and a short and stubby dorsal part; vasa deferentia separately opening into antero-dorsal portion of seminal vesicle; oviducts openings symmetrically into ventral portion of the bursal canal, near its opening into the atrium; mixoploid karyotype, with diploid chromosome portraits of 2n = 2x = 16, and triploid complements of 2n = 3x = 24, with all chromosomes being metacentric. In the context of the various kinds of mixoploidy and the sexualization of specimens, reproductive modalities within the genus Dugesia are shortly discussed.

Conclusion
Molecular, morphological, and karyological markers show that the two populations examined represent members of the genus Dugesia and constitute two new, distinct species.
Utilizing cross-product prior knowledge to rapidly de-risk chemical liabilities in therapeutic antibody candidates
Authors: Jacobitz Alex W. , Rodezno Wilfredo , Agrawal Neeraj J. 
Published: May 2022

AbstractThere is considerable pressure in the pharmaceutical industry to advance better molecules faster. One pervasive concern for protein-based therapeutics is the presence of potential chemical liabilities. We have developed a simple methodology for rapidly de-risking specific chemical concerns in antibody-based molecules using prior knowledge of each individual liability at a specific position in the molecule’s sequence. Our methodology hinges on the development of sequence-aligned chemical liability databases of molecules from different stages of commercialization and on sequence-aligned experimental data from prior molecules that have been developed at Amgen. This approach goes beyond the standard practice of simply flagging all instances of each motif that fall in a CDR. Instead, we de-risk motifs that are common at a specific site in commercial mAb-based molecules (and therefore did not previously pose an insurmountable barrier to commercialization) and motifs at specific sites for which we have prior experimental data indicating acceptably low levels of modification. We have used this approach successfully to identify candidates in a discovery phase program with exclusively very low risk potential chemical liabilities. Identifying these candidates in the discovery phase allowed us to bypass protein engineering and accelerate the program’s timeline by 6 months.
A dengue-like outbreak of unknown aetiology in Pakistan
Authors: Merchant Hamid A. 
Published: May 2022

AbstractThere were recent reports of a mysterious virus spreading in Pakistan causing dengue-like illness with hundreds of cases admitted to hospitals over the winter. The mysterious virus was touted as a new variant of the dengue virus by the local health experts in Pakistan as most patients were tested negative for the dengue virus test despite presenting with dengue-like symptoms. In this letter, we have critically appraised the current situation in Pakistan in an attempt to explain the science and mechanism behind recent dengue-like outbreak, offered suggestions on diagnostic tests and provided recommendations to improve medication safety in Pakistan.
Efficacy and safety of oral pharmacological and supplementary therapies in bladder pain syndrome: a systematic review
Authors: Widyadharma I Putu Eka , Dewi Valentina Tjandra , Wijayanti Ida Ayu Sri , Santosa Kadek Budi 
Published: May 2022

AbstractTreatment goals in bladder pain syndrome (BPS) or interstitial cystitis (IC) focusing on relieving symptoms to improve quality of life and avoiding adverse events (AEs) since curative treatment for BPS/IC is not available. The readily available pharmacologic options for BPS/IC including oral, intravesical, and transdermal therapy. The purpose of this study is to review randomized trial studies over the last 15 years examining the efficacy and safety of oral pharmacological and supplementary therapies for BPS/IC. A systematic search was conducted in PubMed and Medline Library. Only randomized-controlled trials and randomized comparative trials published between 2005 and 2020 on the efficacy and safety of oral therapies for BPS/IC were included. The keywords used were “bladder pain syndrome”, or “interstitial cystitis”, and “random” or “trial”. From 629 articles, nine were included in this review. Oral therapies included consist of cyclosporine A (CyA), amitriptyline, amitriptyline plus alpha lipoic acid (ALA) and omega-3 fatty acids (n-3 PUFA), PD-0299685, sildenafil, pentosan polysulfate sodium (PPS), AQX-1125, and hydrogen-rich water. Among retrieved trials, amitriptyline in combination with ALA and n-3 PUFA, sildenafil, and cyclosporine A proved their efficacy for BPS/IC. Sildenafil was generally well tolerated, while amitriptyline and CyA must be used with caution, the supplementation of ALA/n-3 PUFAs possibly lower dosage of amitriptyline, subsequently reduce its AEs. CyA was superior to PPS but possessed greater AEs. Further studies focusing on etiopathology and phenotype differentiation of this syndrome will greatly contribute to the development of effective therapy.
Anticonvulsant activity and mechanism of actions of fractions of Ipomoea asarifolia (Desr) (Convolvulaceae) ethanol leaf extract
Authors: Chiroma Samaila S. , Nazifi Abdullahi B. , Jamilu Ya’u , Musa Aliyu , Bichi Lawal A. , Chiroma Samaila M. 
Published: May 2022

Abstract
Background
Preparation of Ipomoea asarifolia (Desr) (Convolvulaceae) is widely used in traditional African medicine for the treatments of different kinds of ailments such as syphilis, malaria, convulsions and rheumatism.

Aim
The anticonvulsant properties of fractions of leaf of Ipomoea asarifolia (Desr); n-butanol (BF), chloroform, n-hexane and residual aqueous fractions (RAF) were evaluated on animals.

Results
The RAF at dose of 75 mg/kg (P < 0.01) with 33% quantal protection and 83% protection against mortality is the most active fraction when compared with BF at 300 mg/kg (P < 0.01) with no quantal protection and 83% protection against mortality; the anti-seizure activity could be because of the presence of saponins (23.3%) and flavonoids (43.92%). The RAF may also owes its anticonvulsant activity via GABAergic pathway as flumazenil at 2 mg/kg significantly (P < 0.05) blocked the activity of RAF, via glutamatergic pathway with RAF (P < 0.05) significantly reversing the proconvulsive activity of ketamine at 200 mg/kg as compared to ketamine alone. Opioidergic pathway may also be implicated as naloxone 1 mg/kg significantly (P < 0.05) reduced the anticonvulsant effect of RAF.

Conclusions
BF and RAF of leaf of Ipomoea asarifolia have shown anticonvulsants activities in PTZ-induced seizures. RAF was observed to be the most active fraction of Ipomoea asarifolia extract which probably exerts its action through GABAergic, glutamatergic and opioidergic pathways.
Isothermal microcalorimetry (IMC) calscreener: automated peculiarities of antimicrobial therapy and metabolism depth of multidrug resistant bacteria
Authors: Bayode Michael Tosin , Alabi Mercy Adewumi , Babatunde Olamide Joshua , Sadibo Muyideen Enitan , Lawani Blessing Temitope , Okiti Ayomide Faith , Elabiyi Michael Omoniyi , Lawrence Damilola Israel 
Published: May 2022

AbstractBackgroundThe global development of innovative antimicrobial drugs and drug design techniques has been necessitated by the persistent increase of multidrug resistant infections. Regardless of advances in technology for detecting pathogenic bacteria and their resistance genes (DNA-based assays), most bacteriological studies of infections still use conventional cultural techniques and susceptibility testing as reference standards. Commonly used conventional assays such as the disc diffusion test and broth micro-dilution have been effective in defining pathogen susceptibility and determining the minimum inhibitory concentration of antimicrobial agents. However, they are still prone to error and time consuming, hence, not sufficient in the face of the urgent need for answers to sporadic worldwide disease maladies.Main bodyIn this review, we describe a developing but promising method for gauging/measuring the amount of energy released when a cell is actively metabolizing, which may then be used to calculate the bacterial cell's growth rate. The isothermal microcalorimetry (IMC) calscreener translate heat production of cellular metabolism which is pertinent to the operation of all biological life in demonstrating a more advanced technique for drug design and discovery, especially in the area of pathogen-specific chemotherapy.ConclusionThe IMC calscreener technology is sacrosanct in establishing the heat levels in microwatt to read the metabolic kinematics of biological specimens with emphasis on medically-relevant bacteria within a closed scheme. The application of this technology also looks promising in antimicrobial chemotherapy and metal recovery.