bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strategy for mass production of lytic Staphylococcus aureus bacteriophage pSa-3: contribution of multiplicity of infection and response surface methodology
Authors: Kim Sang Guen , Kwon Jun , Giri Sib Sankar , Yun Saekil , Kim Hyoun Joong , Kim Sang Wha , Kang Jung Woo , Lee Sung Bin , Jung Won Joon , Park Se Chang 
Published: March 2021

Abstract
Background
Antibiotic-resistant bacteria have emerged as a serious problem; bacteriophages have, therefore, been proposed as a therapeutic alternative to antibiotics. Several authorities, such as pharmacopeia, FDA, have confirmed their safety, and some bacteriophages are commercially available worldwide. The demand for bacteriophages is expected to increase exponentially in the future; hence, there is an urgent need to mass-produce bacteriophages economically. Unlike the replication of non-lytic bacteriophages, lytic bacteriophages are replicated by lysing host bacteria, which leads to the termination of phage production; hence, strategies that can prolong the lysis of host bacteria in bacteria–bacteriophage co-cultures, are required.

Results
In the current study, we manipulated the inoculum concentrations of Staphylococcus aureus and phage pSa-3 (multiplicity of infection, MOI), and their energy sources to delay the bactericidal effect while optimizing phage production. We examined an increasing range of bacterial inoculum concentration (2 × 108 to 2 × 109 CFU/mL) to decrease the lag phase, in combination with a decreasing range of phage inoculum (from MOI 0.01 to 0.00000001) to delay the lysis of the host. Bacterial concentration of 2 × 108 CFU/mL and phage MOI of 0.0001 showed the maximum final phage production rate (1.68 × 1010 plaque forming unit (PFU)/mL). With this combination of phage–bacteria inoculum, we selected glycerol, glycine, and calcium as carbon, nitrogen, and divalent ion sources, respectively, for phage production. After optimization using response surface methodology, the final concentration of the lytic Staphylococcus phage was 8.63 × 1010 ± 9.71 × 109 PFU/mL (5.13-fold increase).

Conclusions
Therefore, Staphylococcus phage pSa-3 production can be maximized by increasing the bacterial inoculum and reducing the seeding phage MOI, and this combinatorial strategy could decrease the phage production time. Further, we suggest that response surface methodology has the potential for optimizing the mass production of lytic bacteriophages.
Diagnostic performance of an ultrasensitive HRP2-based malaria rapid diagnostic test kit used in surveys of afebrile people living in Southern Ghana
Authors: Acquah Festus K. , Donu Dickson , Obboh Evans K. , Bredu Dorcas , Mawuli Bernice , Amponsah Jones A. , Quartey Joseph , Amoah Linda E. 
Published: March 2021

Abstract
Background
The Alere™ Malaria Ag P.f Ultra-sensitive RDT (UsmRDT) kit is an HRP2-based malaria rapid diagnostic test (RDT) with enhanced sensitivity relative to the SD Bioline Malaria Ag P.f RDT (mRDT) kit. However, the diagnostic performance of the UsmRDT kit has not been evaluated in Ghana.

Methods
A total of 740 afebrile participants aged between 3 and 88 years old were recruited from the Central and Greater Accra Regions of Ghana during the off-peak malaria season. Axillary body temperature was measured, and a volume of 1 ml venous blood was drawn from each participant. Prior to separating the blood into plasma and packed cell pellets via centrifugation, the blood was spotted onto one UsmRDT and one mRDT kit and also used to prepare thick and thin blood smears as well as filter paper blood spots. Plasmodium falciparum specific polymerase chain reaction (PCR) was performed on gDNA extracted from 100 µl of the whole blood.

Results
The overall positivity rate for microscopy, PCR, UsmRDT and mRDT kit were 20.4%, 40.8%, 31.3% and 30.8%, respectively. Overall, the UsmRDT identified 9.3% (28/302) more PCR positive samples than the mRDT kits. All samples that were negative by the UsmRDT kit were also negative by the mRDT kit. Overall, the sensitivity and specificity of the UsmRDT was 73% (221/302) and 89% (388/436), respectively, while that for the mRDT kit was 58% and 90%, respectively.

Conclusion
Although the UsmRDT kit was not as sensitive as PCR at detecting asymptomatic P. falciparum carriage, it correctly identified P. falciparum in 9.3% of the study participants that were not captured by the mRDT kit. In malaria endemic settings, the UsmRDT would provide an added advantage by identifying more asymptomatic P. falciparum carriers than the mRDT kit for targeted treatment interventions.
Task-shifting to improve asthma education for Malawian children: a qualitative analysis
Authors: Nkhalamba Lovemore , Rylance Sarah , Muula Adamson S. , Mortimer Kevin , Limbani Felix 
Published: March 2021

Abstract
Background
Asthma education, a key component of long-term asthma management, is challenging in resource-limited settings with shortages of clinical staff. Task-shifting educational roles to lay (non-clinical) staff is a potential solution. We conducted a randomised controlled trial of an enhanced asthma care intervention for children in Malawi, which included reallocation of asthma education tasks to lay-educators. In this qualitative sub-study, we explored the experiences of asthmatic children, their families and lay-educators, to assess the acceptability, facilitators and barriers, and perceived value of the task-shifting asthma education intervention.

Methods
We conducted six focus group discussions, including 15 children and 28 carers, and individual interviews with four lay-educators and a senior nurse. Translated transcripts were coded independently by three researchers and key themes identified.

Results
Prior to the intervention, participants reported challenges in asthma care including the busy and sometimes hostile clinical environment, lack of access to information and the erratic supply of medication. The education sessions were well received: participants reported greater understanding of asthma and their treatment and confidence to manage symptoms. The lay-educators appreciated pre-intervention training, written guidelines, and access to clinical support. Low education levels among carers presented challenges, requiring an open, non-critical and individualised approach.

Discussion
Asthma education can be successfully delivered by lay-educators with adequate training, supervision and support, with benefits to the patients, their families and the community. Wider implementation could help address human resource shortages and support progress towards Universal Health Coverage.
Trial registration The RCT was registered in the Pan African Clinical Trials Registry: PACTR201807211617031
B cell‐activating factors in autoimmune pulmonary alveolar proteinosis
Authors: Hirose Masaki , Arai Toru , Sugimoto Chikatoshi , Takimoto Takayuki , Sugawara Reiko , Minomo Shojiro , Shintani Sayoko , Takeuchi Naoko , Katayama Kanako , Inoue Yasushi , Kagawa Tomoko , Kasai Takahiko , Akira Masanori , Inoue Yoshikazu 
Published: March 2021

Abstract
Background
Autoimmune pulmonary alveolar proteinosis (APAP) results from the suppression of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling by a neutralizing autoantibody against GM-CSF. B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are involved in immunoglobulin G production and are overproduced in various autoimmune disorders. We hypothesized that BAFF and/or APRIL levels would be elevated in serum and bronchoalveolar lavage fluid (BALF) and serum and BALF levels of BAFF and APRIL respond to the treatments (whole lung lavage (WLL) or inhalation of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF)) in patients with APAP.

Subjects and methods

BAFF and APRIL levels in serum and BALF from 110 patients with APAP were measured at baseline and during and after treatment, using an enzyme-linked immunosorbent assay kit. We enrolled 34 healthy volunteers as serum cytokine controls, and 13 disease controls for BALF. Associations of BAFF and APRIL levels with clinical measures were assessed to clarify their clinical roles.

Results
In patients with APAP, serum BAFF and APRIL levels were significantly increased relative to healthy volunteers (p < 0.0001 and p < 0.05, respectively), and BALF BAFF and APRIL levels were significantly increased versus disease controls (p < 0.0001 and p < 0.01, respectively). Serum BAFF levels (but not APRIL levels) were significantly correlated with Krebs von den Lungen-6 (KL-6), surfactant protein (SP)-D, SP-A, and lactate dehydrogenase (p < 0.0001). There was no significant correlation between serum BAFF or APRIL levels and anti-GM-CSF autoantibody. BAFF and APRIL were negatively correlated with single-breath diffusion capacity for carbon monoxide (DLco) (p = 0.004) and forced vital capacity (p = 0.04), respectively. BAFF (but not APRIL) in BALF was negatively correlated with vital capacity (p = 0.04) and DLco (p = 0.006). There were significant correlations between disease severity and BAFF levels in serum (p = 0.04) and BALF (p = 0.007). Serum levels of anti-GM-CSF autoantibody, BAFF, and APRIL were not significantly affected by WLL or inhalation of recombinant human GM-CSF.

Conclusions
BAFF and APRIL levels of sera and BALF in APAP were significantly increased compared with healthy volunteer and disease control, and the BAFF and APRIL pathway might have important specific roles in pathogenesis of APAP. Our data suggest a new perspective of future treatment for APAP.
Ethosuximide inhibits acute histamine- and chloroquine-induced scratching behavior in mice
Authors: Gadotti Vinicius M. , Zamponi Gerald W. 
Published: March 2021

AbstractWe have recently reported that the Cav3.2 T-type calcium channel which is well known for its key role in pain signalling, also mediates a critical function in the transmission of itch/pruritus. Here, we evaluated the effect of the clinically used anti-seizure medication ethosuximide, a well known inhibitor of T-type calcium channels, on male and female mice subjected to histaminergic- and non-histaminergic itch. When delivered intraperitoneally ethosuximide significantly reduced scratching behavior of mice of both sexes in response to subcutaneous injection of either histamine or chloroquine. When co-delivered subcutaneously together with either pruritogenic agent ethosuximide was also effective in inhibiting scratching responses in both male and female animals. Overall, our results are consistent with an important role of Cav3.2 T-type calcium channels in modulating histamine-dependent and histamine-independent itch transmission in the primary sensory pathway. Our findings also suggest that ethosuximide could be explored further as a possible therapeutic for the treatment of itch.
Genomic alterations in KMT2 family predict outcome of immune checkpoint therapy in multiple cancers
Authors: Zhang Peng , Huang Yixuan 
Published: March 2021

AbstractImmune checkpoint therapy (ICT) can produce durable antitumor responses in various cancer types; however, the responses are not universal, and the predictive biomarkers are urgently needed. Growing evidence points to a link between epigenetic regulation and anti-tumor immunity, while clinical data on the association of genomic alterations in transcriptional dysregulation-related genes and ICT clinical benefit are lacking. Histone–lysine N-methyltransferase 2 (KMT2) family proteins methylate lysine 4 on the histone H3 tail at important regulatory regions in the genome and thereby impart crucial functions through modulating chromatin structures and DNA accessibility, which is associated with tumorigenesis, mutagenesis, and immune tolerance in various cancers, indicating its possible correlation with the output of immune checkpoint therapy. We hypothesized that genomic mutations in the KMT2 family have the potential to be a novel predictor of immunotherapeutic efficacy. Through integrative cancer genomic analyses of baseline tumor tissues from multiple cohorts involving immunotherapeutic patients, we uncovered a remarkable correlation between KMT2 family mutation and better immune checkpoint therapy responses in multiple patient cohorts. Then, we gathered all the independent ICT-treated datasets as a combination cohort consisted of 418 patients. Significant enrichment of KMT2 family genomic alterations in responding tumors was observed (odds ratio = 2.60, P value = 1.67e−04). This work distinguished the mutations in the KMT2 family as a potential predictor of favorable ICT response in multiple cancers, highlighting the importance of genomic profiling in immunotherapy.
Incident gout and weight change patterns: a retrospective cohort study of US adults
Authors: Bai Lu , Zhou Jian-Bo , Zhou Tao , Newson Roger B. , Cardoso Marly Augusto 
Published: March 2021

Abstract
Background
Although the relationship between obesity and incident gout has been clarified, the influence of weight changes during the transition from early adulthood to midlife and the different weight change patterns in specific age ranges on the incidence of gout in later life remain unknown. Therefore, we aimed to investigate the association between weight change patterns across adulthood and incident gout.

Methods
Using data from the National Health and Nutrition Examination Survey (NHANES), we categorized individuals into four weight change patterns: those who remained obese (stable obese), those who moved from a non-obese body mass index (BMI) to an obese BMI (gaining), those who moved from an obese BMI to a non-obese BMI (losing), and those who remained non-obese (stable non-obese). Incident gout reflected its occurrence over the 10-year follow-up from the recalled midlife weight measure to the time of this survey. Hazard ratios (HRs) and 95% confidence intervals relating weight change patterns to incident gout over the 10-year follow-up period were calculated using Cox models adjusted for covariates. The hypothetical population attributable fraction (PAF) for the weight change patterns was calculated.

Results
Among our sample of adults aged 40–74 years at their midlife weight measure (n = 11,079), 320 developed gout. The highest risk of incident gout was found for participants with the stable obese pattern (HR 1.84; 1.08–3.14) and not for participants who remained stable non-obese during adulthood. Moreover, gaining weight was a significant risk factor for incident gout (HR 1.65; 1.19–2.29). No significant associations were found between losing weight change patterns and the risk of gout during the study period. If participants who gained weight had become non-obese during the 10-year follow-up, an estimated 3.2% (95% CI 0–6.3) of observed gout cases could have been averted. In addition, if the population had maintained a normal BMI, 32.9% (95% CI 18.2–44.9) cases could have been prevented during the 10 years.

Conclusions
Gaining weight over adulthood was associated with an increased risk of gout. These findings have highlighted that maintaining non-obese weight and weight loss across adulthood is essential for the prevention and treatment of gout in adult life.
Predictors of the length of stay of psychiatric inpatients: protocol for a systematic review and meta-analysis
Authors: Carranza Navarro Farid , Álvarez Villalobos Neri Alejandro , Contreras Muñoz Andrea Muriel , Guerrero Medrano Andrea Fernanda , Tamayo Rodríguez Natalia Sofía , Saucedo Uribe Erasmo 
Published: March 2021

Abstract
Background
Length of stay (LOS) for inpatient psychiatric services is an important factor with serious drawbacks when it is extended more than needed. Impacts on economy, social functioning, and stigma can hamper improvement and affect the patients’ experiences on future mental healthcare. Predictions of which patients have a higher chance for prolonged LOS have been extensively researched. Previous systematic reviews found consistent predictors of both longer and shorter LOS. However, they do not provide an estimate from the pooled effect sizes. Furthermore, to our knowledge, there is no meta-analysis on the influence of these factors. The primary objective of this study will be to provide point estimates on the effect sizes of all studied predictors of the LOS of psychiatric inpatients.

Methods
We will conduct a systematic search in PubMed, MEDLINE, EMBASE, and PsycINFO for observational studies evaluating the effect size of independent factors on the length of stay of psychiatric inpatients. Prospective and retrospective cohorts that assess the influence of predictors through the reporting of standardized regression coefficients will be included. We will provide a qualitative synthesis of the findings from each study and perform a meta-analysis from pooled regression coefficients that were adjusted for other variables or confounders in order to obtain a point estimate and confidence interval for all factors extracted from the included studies.

Discussion
The results from this study may provide more accurate predictions for mental health institutions, psychiatrists, mental health service providers, patients, and families on the prognosis regarding the length of stay for needed inpatient care. This information may be used to anticipate individuals with a higher chance for prolonged hospitalization to plan the necessary interventions for these specific situations. Considering both the benefits and disadvantages of longer and shorter stays, the pooled estimates for independent factors may be used by mental healthcare providers and patients for informed decision-making. The results from this study will also update results presented in previous studies and identify the strengths and limitations from the current available evidence.

Systematic review registration
PROSPERO ID CRD42020172840
Predictive biomarkers of anti-PD-1/PD-L1 therapy in NSCLC
Authors: Niu Mengke , Yi Ming , Li Ning , Luo Suxia , Wu Kongming 
Published: March 2021

AbstractImmunotherapy, especially anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) treatment has significantly improved the survival of non-small cell lung cancer (NSCLC) patients. However, the overall response rate remains unsatisfactory. Many factors affect the outcome of anti-PD-1/PD-L1 treatment, such as PD-L1 expression level, tumor-infiltrating lymphocytes (TILs), tumor mutation burden (TMB), neoantigens, and driver gene mutations. Further exploration of biomarkers would be favorable for the best selection of patients and precisely predict the efficacy of anti-PD-1/PD-L1 treatment. In this review, we summarized the latest advances in this field, and discussed the potential applications of these laboratory findings in the clinic.
Fine-scale behaviour of the Lusitanian toadfish assessed in situ with the AccelTag
Authors: Pereira Tadeu J. , Almeida Pedro R. , Quintella Bernardo R. , Gronningsaeter Aage , Costa Maria J. , Marques João P. , Costa José L. 
Published: March 2021

Abstract
Background
Three-axis acceleration sensor acoustic transmitters (AccelTag) programmed to identify specific acceleration patterns associated with particular behaviours (e.g., burrowing, attack) were used to study some aspects of the ecology of the Lusitanian toadfish Halobatrachus didactylus (Bloch & Schneider 1801). The AccelTag combines the features of archival tags (records acceleration in all three directions measuring also roll-independent pitch/tilt angle and roll around the fish’s axis) and acoustic transmitters. Therefore, this tag can autonomously identify and record specific signatures (i.e., behaviour patterns) of different movements transmitting autonomously and periodically the data to an acoustic biotelemetry receiver. Lusitanian toadfish is a subtropical marine teleost confined to estuaries in its northern limit of distribution due to thermal constraints. During 2010 (August and October), 24 toadfish were captured, tagged with the AccelTag and released in the Mira estuary, SW coast of Portugal, where an array of underwater automatic acoustic biotelemetry receivers was deployed.

Results
Around 40% of AccelTag transmissions from tagged fish that stayed in the study area were logged by the acoustic receiver array. The Lusitanian toadfish exhibited low activity during late summer and early autumn (< 3% of time active). The tidal stage and time of day were important factors that influenced the species behaviour and activity. Increased burrowing and re-burrowing movements were registered during spring tides, while attacks prevailed on neap tides and during the night. The tidal cycle only influenced toadfish behaviour and activity in interaction with time of day, with more attacks and higher levels of activity during nocturnal high tides.

Conclusions
Higher activity levels and attacks displayed by the Lusitanian toadfish during the night, at high tide periods and during Spring tides are considered to be associated with increased activity and vulnerability of its prey during these periods. The AccelTag proved to be a powerful tool to assess and monitor the activity and fine-scale behaviour of fish in situ. This technology is particularly suited for fish species with biological and ecological features similar to Lusitanian toadfish, i.e., resident species with low activity levels and behaviours with a distinct 3D acceleration signature.
Palaeobotanical and biomarker evidence for Early Permian (Artinskian) wildfire in the Rajmahal Basin, India
Authors: Murthy Srikanta , Mendhe Vinod Atmaram , Uhl Dieter , Mathews Runcie Paul , Mishra Vivek Kumar , Gautam Saurabh 
Published: March 2021

AbstractThis study provides a combined analysis on the palynology, fossil charcoal and biomarkers of the subsurface coal deposits from a borehole RMB #2 drilled at the Dhulia Coal Block, Rajmahal Basin, India, in attempts to establish the chronology of sedimentation and to propose palaeobotanical as well as geochemical evidence for the occurrence of wildfires in these sediments. The palynological investigation suggests aScheuringipollenites barakarensispalynoassemblage from the lower Barakar Formation, dated as Artinskian (Early Permian) in age. This assemblage reveals the dominance of Glossopteridales and sub-dominance of taxa belonging to Cordaitales and Coniferales. Fossil charcoal in sediments is usually recognized as a direct indicator for the occurrence of palaeo-wildfires. More data involving the anatomical features of fossil charcoal analyzed by Field Emission Scanning Electronic Microscope broaden our knowledge on Early Permian wildfires from the peninsula of India. The studied macroscopic charcoal fragments exhibit anatomical details such as homogenized cell walls, uniseriate simple and biseriate alternate pitting on tracheid walls and rays of varying heights pointing to a gymnospermous wood affinitity. The excellent preservation of charcoal fragments, shown by their large sizes and almost unabraded edges, suggests a parautochthonous origin. The embedded biomarker study performed for charcoal sediments and its characterization demonstrate the presence ofn-alkanes, isoprenoids, terpenoids and aromatic compounds. A bimodal distribution pattern ofn-alkanes with a Cmaxatn-C25is identified. Diterpenoids and pentacyclic terpenoids are identified, indicating the input of an early conifer vegetation and bacterial activity, respectively. The identified polyaromatic hydrocarbon (PAH) compounds, together with the charcoal fragments, clearly suggest that repeated wildfire events occurred during the deposition of these Artinskian sediments in the Rajmahal Basin.