bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mass Flow Control Strategy for Maximum Energy Extraction in Thermal Energy Storage Tanks
Authors: Montoya-Marquez Orlando , Acevedo-Parra H. R. , Valdivia Leonardo J. 
Published: November 2024

Abstract
This paper introduces an experimental approach to enhance thermal energy storage (TES) tank performance by employing a novel control strategy and an automatic flow valve. The valve adjusts mass flow to minimize heat loss and maximize useful heat within a specified input–output temperature range. Experiments were conducted indoors, simulating input heat via an electric heating element, and adhering to ANSI/ASHRAE 93-2010 standards. In the proposed control strategy, the set point is self-regulated based on an input value which in this case is the heat introduced into the TES system. In this way, when there is more input heat available, the mass flow will increase to obtain more useful heat at the output and, on the contrary, when there is less heat available, the mass flow will be reduced to obtain greater exergy. A comparison between this strategy and conventional on–off control systems was conducted, evaluating their performance based on useful heat obtained over an 8-h period with varying input heat levels. Results demonstrate that the proposed flow control methodology consistently outperforms on–off control, achieving a maximum 13.56% increase in useful heat under optimal conditions. This underscores the effectiveness of the novel control strategy in maximizing thermal energy storage tank efficiency.
The Effect of Corrective Exercises on Ground Reaction Forces in Male Students With Upper Crossed Syndrome During Throwing
Authors: Sakinepoor Ainollah , Degens Hans , Ahmadi Poria , Nazari Sagher , Mazidi Maryam 
Published: November 2024

Purpose: Poor posture has a negative impact on physical capability and is associated with changes in biomechanics and motor control. The purpose of this study was to assess the effect of corrective exercises on ground reaction forces (GRFs) in male student handball players with upper crossed syndrome (UCS) during throwing. Methods: Thirty male handball students with UCS participated in this single-blind randomized controlled trial (IRCT20200622047888N2; IR.HUMS.REC.1402.135). Fifteen received an 8-week corrective exercise intervention (exercise-intervention group [EG]), consisting of exercise targeting muscles involved in the UCS, and 15 served as the control group (CG). During handball throwing, GRF was measured by force plate. The forward head and rounded shoulder angles were measured with a photogrammetric method. All measurements were repeated 8 weeks later. Results: Significant interactions for virtually all parameters indicated that changes over 8 weeks differed between the CG and EG. A reduction in GRFs and a delayed occurrence of peak GRFs were observed in the EG, but not in the CG (P < .05). This was accompanied by a significant reduction in forward head (P < .03; effect size: 0.87; 95% confidence interval, −2.34 to 0.13), rounded shoulder (P < .05; effect size: 0.68; 95% confidence interval, 0.32 to 1.22) and thoracic kyphosis (P < .02; effect size: 0.64; 95% confidence interval, 0.54 to 1.25) angles in the EG (P < .05) with no significant change over 8 weeks in the CG. Conclusion: Corrective exercises targeting muscles directly involved in UCS induces functional and postural improvements in male student handball players with UCS.
Integration of horizontally acquired light-harvesting genes into an ancestral regulatory network in the cyanobacterium
Acaryochloris marina
MBIC11017
Authors: Ulrich Nikea J. , Miller Scott R. 
Published: November 2024

ABSTRACT

The acquisition of new capabilities by horizontal gene transfer (HGT) shapes the distribution of traits during microbial diversification. In the Chlorophyll (Chl)
d
-producing cyanobacterium
Acaryochloris marina
, the genes involved in the production and disassembly of the light-harvesting phycobiliprotein phycocyanin (PC) were lost in the
A. marina
common ancestor but then subsequently regained via HGT in
A. marina
strain MBIC11017. However, it remains unknown how the HGT-acquired PC genes in MBIC11017 have been reintegrated into its existing regulatory network after tens of millions of years since their loss. Here, we investigated potential mechanisms of regulatory assimilation of PC genes by comparing the transcriptomes of
A. marina
strain MBIC11017 and a PC-lacking close relative under both low irradiance far-red light and high irradiance white light. We found that PC assembly and degradation processes have been re-assimilated into a conserved ancestral response to high light. Further, we identified putative regulatory elements that were likely co-transferred with PC genes and could be recognized by
A. marina
’s pre-existing light response machinery. This study offers insights into how HGT-acquired genes can be reintegrated into an existing transcriptional regulatory network that has evolved in their absence.

IMPORTANCE

Horizontal gene transfer, the asymmetric movement of genetic information between donor and recipient organisms, is an important mechanism for acquiring new traits. In order for newly acquired gene content to be retained, it must be integrated into the genetic repertoire and regulatory networks of the recipient cell. In a strain of the Chlorophyll
d
-producing cyanobacterium
Acaryochloris marina
, the recent reacquisition of the genes required to produce the light-harvesting pigment phycocyanin offers a rare opportunity to understand the mechanisms underlying the regulatory assimilation of an acquired complex trait in bacteria. The significance in our research is in characterizing how an ancestrally lost, complex trait can be reintegrated into a conserved regulatory network, even after millions of years.
RNAseq and targeted metabolomics implicate RIC8 in regulation of energy homeostasis, amino acid compartmentation, and asexual development in
Neurospora crassa
Authors: Quinn Monique , Carrillo Alexander J. , Halilovic Lida , Borkovich Katherine A. 
Published: November 2024

ABSTRACT

Heterotrimeric G protein signaling pathways control growth and development in eukaryotes. In the multicellular fungus
Neurospora crassa
, the guanine nucleotide exchange factor RIC8 regulates heterotrimeric Gα subunits. In this study, we used RNAseq and liquid chromatography-mass spectrometry (LC-MS) to profile the transcriptomes and metabolomes of
N. crassa
wild type, the Gα subunit mutants Δ
gna-1
and Δ
gna-3
, and Δ
ric8
strains. These strains exhibit defects in growth and asexual development (conidiation), with wild-type and Δ
gna-1
mutants producing hyphae in submerged cultures, while Δ
gna-3
and Δ
ric8
mutants develop conidiophores, particularly in the Δ
ric8
mutant. RNAseq analysis showed that the Δ
gna-1
mutant possesses 159 mis-regulated genes, while Δ
gna-3
and Δ
ric8
strains have more than 1,000 each. Many of the mis-regulated genes are involved in energy homeostasis, conidiation, or metabolism. LC-MS revealed changes in levels of primary metabolites in the mutants, with several arginine metabolic intermediates impacted in Δ
ric8
strains. The differences in metabolite levels could not be fully explained by the expression or activity of pathway enzymes. However, transcript levels for two predicted vacuolar arginine transporters were affected in Δ
ric8
mutants. Analysis of arginine and ornithine levels in transporter mutants yielded support for altered compartmentation of arginine and ornithine between the cytosol and vacuole in Δ
ric8
strains. Furthermore, we validated previous reports that arginine and ornithine levels are low in wild-type conidia. Our results suggest that RIC8 regulates asexual sporulation in
N. crassa
at least in part through altered expression of vacuolar transporter genes and the resultant mis-compartmentation of arginine and ornithine.

IMPORTANCE

Resistance to inhibitors of cholinesterase-8 (RIC8) is an important regulator of heterotrimeric Gα proteins in eukaryotes. In the filamentous fungus
Neurospora crassa
, mutants lacking ric8 undergo inappropriate asexual development (macroconidiation) during submerged growth. Our work identifies a role for RIC8 in regulating expression of transporter genes that retain arginine and ornithine in the vacuole (equivalent of the animal lysosome) and relates this function to the developmental defect. Arginine is a critical cellular metabolite, both as an amino acid for protein synthesis and as a precursor for an array of compounds, including proline, ornithine, citrulline, polyamines, creatine phosphate, and nitric oxide. These results have broad relevance to human physiology and disease, as arginine modulates immune, vascular, hormonal, and other functions in humans.
Similarities and distinctions in the activation of the
Candida glabrata
Pdr1 regulatory pathway by azole and non-azole drugs
Authors: Conway Thomas P. , Vu Bao Gia , Beattie Sarah R. , Krysan Damian J. , Moye-Rowley W. Scott 
Published: November 2024

ABSTRACT

Incidences of fluconazole (FLC) resistance among
Candida glabrata
clinical isolates are a growing issue in clinics. The pleiotropic drug response network in
C. glabrata
confers azole resistance and is defined primarily by the Zn
2
Cys
6
zinc cluster-containing transcription factor Pdr1 and target genes such as
CDR1
, which encodes an ATP-binding cassette transporter protein thought to act as an FLC efflux pump. Mutations in the
PDR1
gene that render the transcription factor hyperactive are the most common cause of fluconazole resistance among clinical isolates. The phenothiazine class drug fluphenazine and a molecular derivative, CWHM-974, which both exhibit antifungal properties, have been shown to induce the expression of Cdr1 in
Candida
spp. We have used a firefly luciferase reporter gene driven by the
CDR1
promoter to demonstrate two distinct patterns of
CDR1
promoter activation kinetics: gradual promoter activation kinetics that occur in response to ergosterol limitations imposed by exposure to azole and polyene class antifungals and a robust and rapid
CDR1
induction occurring in response to the stress imposed by fluphenazines. We can attribute these different patterns of
CDR1
induction as proceeding through the promoter region of this gene since this is the only segment of the gene included in the luciferase reporter construct. Genetic analysis indicates that the signaling pathways responsible for phenothiazine and azole induction of
CDR1
overlap but are not identical. The short time course of phenothiazine induction suggests that these compounds may act more directly on the Pdr1 protein to stimulate its activity.

IMPORTANCE

Candida glabrata
has emerged as the second-leading cause of candidiasis due, in part, to its ability to acquire high-level resistance to azole drugs, a major class of antifungal that acts to block the biosynthesis of the fungal sterol ergosterol. The presence of azole drugs causes the induction of a variety of genes involved in controlling susceptibility to this drug class, including drug transporters and ergosterol biosynthetic genes such as ERG11. We found that the presence of azole drugs leads to an induction of genes encoding drug transporters and ERG11, while exposure of
C. glabrata
cells to antifungals of the phenothiazine class of drugs caused a much faster and larger induction of drug transporters but not ERG11. Coupled with further genetic analyses of the effects of azole and phenothiazine drugs, our data indicate that these compounds are sensed and responded to differentially in the yeast cell.
Etoposide targets 2A protease to inhibit enterovirus 71 replication
Authors: Liang Qinqin , Shi Sai , Zhang Qingjie , Wang Yaxin , Ye Sheng , Xu Binghong 
Published: November 2024

ABSTRACT

Enterovirus 71 (EV71) is a major pathogen that causes hand, foot, and mouth disease (HFMD) in infants and children. Notably, no clinically approved drugs specifically target EV71. The EV71 2A protease (2A
pro
), a cysteine protease produced by the virus, is essential for the virus’ replication and has a significant impact on the functioning of host cells. Thus, it presents a valuable target for the discovery of antiviral medications. In this study, based on the monomers and their derivatives in the Library of Traditional Chinese Medicine (TCM), we performed virtual screening and biological experiments. We identified a derivative of a traditional herbal monomer, Etoposide, commonly isolated from the roots and rhizomes of
Podophyllum
spp. Etoposide inhibited replication of EV71 A, B, C, and CVA16 viruses in a concentration-dependent manner in a variety of cell lines with minimal cytotoxicity. Furthermore, both molecular dynamics simulations and site-directed mutagenesis assays revealed that Etoposide inhibited the activity of the EV71 2A protease by mainly binding to two residues, Y89 and P107. The findings indicate that Etoposide serves as a promising inhibitor of the EV71 2A
pro
, demonstrating strong antiviral properties and positioning itself as a formidable candidate for clinical trials against EV71.

IMPORTANCE

We first used a drug screening approach focused on monomeric compounds and their derivatives from traditional Chinese medicine to identify an EV71 2A
pro
inhibitor—Etoposide. We then performed biological experiments to validate that Etoposide suppresses the replication of the EV71 virus in a concentration-dependent manner with minimal cytotoxicity to various cell lines. Remarkably, it shows inhibitory activity against EV71 A, B, C, and CVA16, suggesting that Etoposide may be a potential broad-spectrum inhibitor. We revealed a novel mechanism that Etoposide inhibits EV71 proliferation by targeting 2A
pro
, and the interactions with Y89 and P107 are of great importance. The findings suggest that Etoposide serves as a promising inhibitor of EV71 2A
pro
, demonstrating significant antiviral properties. It stands out as a strong candidate for broad-spectrum applications in clinical research.
Acquired factor V inhibitor treated with rituximab
Authors: Ansari Faisal , Lee Yurhee , Ansari Umar , Kim Phyllis 
Published: November 2024

Acquired factor V (FV) inhibitors are extremely rare and present with a broad spectrum ranging from asymptomatic laboratory anomalies to life-threatening critical bleeds. The overall rarity along with the heterogeneity of clinical presentations poses a challenge in diagnosis. There is currently no standard of care immunosuppressive therapy (IST) in these settings. Most patients in the literature receive multiple agents, including but not limited to combinations of IST and/or recombinant products.Here, we present a case of a man in his 50s who initially presented with oozing at peripheral IV and tracheostomy sites with intermittent epistaxis. He was later found to have an FV activity level of less than 1% and an FV inhibitor titre of 184 Bethesda units/mL. The patient was initially stabilised with fresh frozen plasma, platelets and tranexamic acid and treated with intravenous immunoglobulin and glucocorticoids. However, this resulted in only mild improvement in his coagulation studies. He was then treated with weekly doses of rituximab for 4 weeks with ongoing glucocorticoids without complications. This adds to the growing literature on rituximab as a possible treatment option for acquired FV inhibitors.
Efficacy and acceptability of lurasidone for bipolar depression: a systematic review and dose–response meta-analysis
Authors: Lin Yu-Wei , Chen Yang-Chieh Brian , Hung Kuo-Chuan , Liang Chih-Sung , Tseng Ping-Tao , Carvalho Andre F , Vieta Eduard , Solmi Marco , Lai Edward Chia-Cheng , Lin Pao-Yen , Hsu Chih-Wei , Tu Yu-Kang 
Published: November 2024

Question
The optimal dose of lurasidone for bipolar depression is unclear. This study examined its dose–response relationship for efficacy, acceptability, and metabolic/endocrine profiles.

Study selection and analysis
Five databases and grey literature published until 1 August 2024, were systematically reviewed. The outcomes included efficacy (changes in depression, anxiety, clinical global impression, disability and quality of life), acceptability (dropout, manic switch, suicidality and side effects) and metabolic/endocrine profiles (changes in body weight, glucose, lipid and prolactin levels). Effect sizes were calculated using a one-step dose–response meta-analysis, expressed as standardised mean differences (SMDs), risk ratios (RRs) and mean differences (MDs) with 95% CIs.

Findings
Five randomised clinical trials (2032 patients, mean treatment duration 6 weeks) indicated that the optimal therapeutic dose of lurasidone (40–60 mg) improved depression (50 mg: SMD −0.60 (95% CI −0.30, –0.89)), anxiety (50 mg: −0.32 (95% CI −0.21, –0.42)), clinical global impression (50 mg: −0.67 (95% CI −0.30, –1.03)) and disability (50 mg: −0.38 (95% CI −0.08, –0.69)). Side effects increased with higher doses (50 mg: RR 1.15 (95% CI 1.05, 1.25); 100 mg: 1.18 (95% CI 1.02, 1.36)), but dropout, manic switch and suicidality did not show a dose–effect relationship. Weight increased at doses<60 mg (40 mg: MD 0.38 (95% CI 0.16, 0.60) kg), while blood glucose levels rose at doses>70 mg (100 mg: 3.16 (95% CI 0.76, 5.57) mg/dL). Prolactin levels increased in both males (50 mg: 3.21 (95% CI 1.59, 4.84) ng/mL; 100 mg: 5.61 (95% CI 2.42, 8.81)) and females (50 mg: 6.64 (95% CI 3.50, 9.78); 100 mg: 5.33 (95% CI 0.67, 10.00)).

Conclusions
A daily dose of 40–60 mg of lurasidone is a reasonable choice for bipolar depression treatment.

Trial registration number
INPLASY202430069.
Transcatheter aortic valve implantation versus surgical aortic valve replacement in Chinese patients with intermediate and high surgical risk for aortic stenosis: a decision analysis on effect, affordability and cost-effectiveness
Authors: Chen Tongfeng , Gao Chuanyu , Chen Chong , Zhao Yipin , Cheng Jiangtao , Guo Xiaoyan , Hu Dan , Liu Chang , Liu Yuhao 
Published: November 2024

ObjectiveExamine the cost-effectiveness of transcatheter aortic valve implantation (TAVI) versus surgical aortic valve replacement (SAVR) for Chinese patients with severe aortic stenosis (AS) at intermediate and high surgical risk.DesignA two-phase model, comprising a 1-month decision tree to simulate perioperative outcomes and a 5-year Markov model with monthly cycles to simulate long-term outcomes, has been developed to evaluate the cost-effectiveness of TAVI compared with SAVR for Chinese patients with AS at intermediate and high risk. The event rates for both phases are sourced from the Placement of Aortic Transcatheter Valves IA and IIA trials, while the cost inputs and utility values are sourced from local sources or published literature. Adjustments for inflation were made using consumer price indexes for healthcare to enhance precision. To ensure the reliability and robustness of the model, sensitivity analyses were conducted to assess their impact on outcomes.SettingChina healthcare system perspective.ParticipantsA hypothetical cohort of Chinese patients with AS in intermediate and high surgical risk.InterventionsTAVI versus SAVR.Outcome measuresCost, quality-adjusted life-years (QALYs), life-years gained and incremental cost-effectiveness Ratio (ICER).ResultFor both intermediate- and high-risk AS patients, offering TAVR resulted in high healthcare costs but moderate benefits compared with SAVR. Specifically, in the intermediate-risk population, TAVR led to a 0.34 QALY increase over SAVR, with an incremental cost of $16 707.58, resulting in an ICER of $49 176.60/QALY. Similarly, in the high-risk population, TAVR showed a 0.15 QALY increase over SAVR, with an incremental cost of $18 093.52, leading to an ICER of $122 696.37/QALY. However, both ICERs exceeded the willingness-to-pay threshold of $37 654.50/QALY. Sensitivity analyses confirmed the model’s stability under parameter uncertainty.ConclusionTAVI was deemed not cost-effective compared with SAVR for patients with AS at intermediate or high surgical risk in the Chinese healthcare system. Lowering valve costs was considered an effective approach to improve the cost-effectiveness of TAVI.
Uses of private health provider data for governance in low-income and middle-income countries: results from a scoping review
Authors: Faddoul Alix , Montagu Dominic , Kanneganti Sneha , O’Hanlon Barbara 
Published: November 2024

This work grew from an interest in understanding how private data are used for health system governance in low-income and middle-income countries (LMICs).ObjectiveWe conducted a scoping review to understand how the public sector collects routine data from the private health sector and uses it for governance purposes. The private health sector was defined to include both formal and informal, for-profit or non-profit, actors delivering healthcare services.FindingsWe identified 4014 individual English language studies published between 2010 and 2021. We reviewed titles and abstracts of all, with 50% reviewed by two authors to ensure a common application of inclusion criteria. 89 studies were selected for review in full; following this, 26 articles were included in the final selection as they directly report on the use of routine private sector data for governance in LMICs. Only English language studies were included, limiting the scope of possible conclusions.ResultsData were most commonly collected by the Ministry of Health or a subministerial office, with extraction from District Health Information System 2 specifically cited for three studies. 16 studies collected data on infrastructure and distribution, 15 on service delivery, 12 on health financing, 7 on pharmaceuticals and other consumables, 4 on health workforce, 4 on quality of care and 4 on epidemic surveillance.ConclusionThe studies identified provide examples of the public sector’s capacity to collect and use data routinely collected from the private sector to perform essential governance functions. The paucity of studies identified is an indication that more attention is needed to ensure that this key area of health system governance is undertaken and that lessons learnt are shared. This review provides insights to understanding private sector health data collection and use for governance in LMICs, and for guiding activities to assess and improve this according to country context and capacity.