bluuebunny/crossref_metadata_2025_split huggingface dataset:
The
Candida albicans
ζ-crystallin homolog Zta1 promotes resistance to oxidative stress
Authors: Gandra Rafael M. , Johnson Chad J. , Nett Jeniel E. , Konopka James B. 
Published: November 2023

ABSTRACT

The fungal pathogen
Candida albicans
is capable of causing lethal infections in humans. Its pathogenic potential is due in part to the ability to resist various stress conditions in the host, including oxidative stress. Recent studies showed that a family of four flavodoxin-like proteins (Pst1, Pst2, Pst3, Ycp4) that function as quinone reductases promotes resistance to oxidation and is needed for virulence. Therefore, in this study, Zta1 was examined because it belongs to a structurally distinct family of quinone reductases that are highly conserved in eukaryotes and have been called the ζ-crystallins. The levels of Zta1 in
C. albicans
rapidly increased after exposure to oxidants, consistent with a role in resisting oxidative stress. Accumulation of reactive oxygen species (ROS) was significantly higher in cells lacking
ZTA1
upon exposure to quinones and other oxidants. Furthermore, the deletion of
ZTA1
in a mutant lacking the four flavodoxin-like proteins, resulted in further increased susceptibility to quinones, indicating that these distinct quinone reductases work in combination. These results demonstrate that Zta1 contributes to
C. albicans
survival after exposure to oxidative conditions, which increases the understanding of how
C. albicans
resist stressful conditions in the host.

IMPORTANCE

Candida albicans
is an important human pathogen that can cause lethal systemic infections. The ability of
C. albicans
to colonize and establish infections is closely tied to its highly adaptable nature and capacity to resist various types of stress, including oxidative stress. Previous studies showed that four
C. albicans
proteins belonging to the flavodoxin-like protein family of quinone reductases are needed for resistance to quinones and virulence. Therefore, in this study, we examined the role of a distinct type of quinone reductase, Zta1, and found that it acts in conjunction with the flavodoxin-like proteins to protect against oxidative stress.
Lactobacillus
-driven feed fermentation regulates microbiota metabolism and reduces odor emission from the feces of pigs
Authors: Zhang Dongyan , Ji Haifeng , Wang Sixin , Liu Yajuan , Chen Meixia , Liu Hui 
Published: November 2023

ABSTRACT

Fermentation by
Lactobacillus
can increase the nutritional value of feed, which is advantageous for pig production. However, the effects of
Lactobacillus
-driven feed fermentation on the emission of odors from pig feces are unclear. Here, we evaluated how feed fermentation by
Lactobacillus
affects the concentration of odor molecules in feces (CO
2
, NH
3
, H
2
S, indole, and skatole) and analyzed the changes in fecal microbiota and metabolites during fecal storage. Pigs reared on fermented feed had a higher average daily gain (ADG) and lower feed-to-gain (
F
/
G
) ratio than the control group. By the 3rd and 5th days, the concentration of CO
2
in feces from pigs in the fermentation group significantly decreased, and the contents of H
2
S, NH
3
, and skatole in the fermentation group were significantly lower than those in the control group on the 1st, 3rd, and 5th days of fecal storage. The fermentation group exhibited a higher Bacteroidetes abundance on the 3rd and 5th days. With prolonged fecal storage, the fermentation group exhibited a higher abundance of
Weissella
and
Lactobacillus
and a lower abundance of
Streptococcus
. The
Lactobacillus
fermentation group also showed lower levels of secondary amino acid metabolites, such as 6-hydroxyhexanoic acid and 5-aminopentanoic acid. The pure strain
Weissella cibaria
ZWC030, which could inhibit the production of skatole
in vitro
, was successfully isolated from the fermentation group. Overall, the study revealed the interrelationships among fecal microbiota, metabolites, and odor molecules. The findings provide a new avenue for the application of
Lactobacillus
-driven feed fermentation to promote ADG, decrease the
F
/
G
ratio in pigs during growth, and reduce environmental pollution.

IMPORTANCE

Our present study showed that dietary supplementation with feed fermented by
Lactobacillus
could promote the growth performance of pigs, regulate the microbiota, and inhibit the growth of harmful bacteria. It could prevent the accumulation of toxic substances and reduce odor emission from pig feces, thereby reducing environmental pollution. In addition, one key triumph of the present study was the isolation of
Weissella cibaria
ZWC030, and the strain could inhibit the production of skatole
in vitro
in our present results.
Antiparasitic nitazoxanide potentiates colistin against colistin-resistant
Acinetobacter baumannii
and
Escherichia coli in vitro
and
in vivo
Authors: Xu Mengxin , Yao Zhuocheng , Kong Jingchun , Tang Miran , Liu Qi , Zhang Xiaotuan , Shi Shiyi , Zheng Xiangkuo , Cao Jianming , Zhou Tieli , Wang Zhongyong 
Published: November 2023

ABSTRACT

Multidrug-resistant Gram-negative bacterial infections pose a serious threat to public health and safety. Colistin is a line of defense against these infections, but colistin-resistant (COL-R) bacteria have emerged worldwide. This study aimed to explore the synergistic potential of nitazoxanide (NTZ) in combination with colistin for the treatment of COL-R
Acinetobacter baumannii
and
Escherichia coli
strains
in vitro
and
in vivo
. The checkerboard and time-killing assays indicated that NTZ in combination with colistin exhibited potent antibacterial activity against COL-R
A. baumannii
and COL-R
E. coli
. The antibiofilm activity measured by crystal violet staining and scanning electron microscopy combined with a confocal laser scanning microscope revealed that the combination of NTZ and colistin could inhibit biofilm formation and eradicate the formed biofilm. This study also demonstrated that the application of this drug combination to an
in vivo
infection model significantly increased the survival rate of
Galleria mellonella
larvae. Hemolysis tests revealed that the combination of NTZ and colistin showed no cytotoxicity. Altogether, the combination of NTZ and colistin showed promising synergistic antibacterial and antibiofilm effects
in vitro
and
in vivo
. This combination might be used as an alternative therapy for treating COL-R
A. baumannii
and COL-R
E. coli
infections.

IMPORTANCE

Colistin is used as a last resort in many infections caused by multidrug-resistant Gram-negative bacteria; however, colistin-resistant (COL-R) is on the rise. Hence, it is critical to develop new antimicrobial strategies to overcome COL-R. We found that nitazoxanide (NTZ) combined with colistin showed notable synergetic antibacterial activity. These findings suggest that the NTZ/colistin combination may provide an effective alternative route to combat COL-R
A. baumannii
and COL-R
Escherichia coli
infections.
Supplemental Material: Early uplift and exhumation of the Tanggula granitoid pluton since the Late Cretaceous: Implications for the stepwise topographic growth model in the eastern Qiangtang terrane
Authors: Lu Lu , et al.  
Published: November 2023

<p>Table S1: A compilation of low-temperature thermochronology (LTT) data in the eastern Qiangtang terrane. Table S2: Apatite U-Pb dating results for samples from the Tanggula granitoid pluton. Table S3: Biotite <sup>40</sup>Ar-<sup>39</sup>Ar furnace step-heating analytical results for samples from the Tanggula granitoid pluton. Table S4: K-feldspar <sup>40</sup>Ar-<sup>39</sup>Ar furnace step-heating analytical results for samples from the Tanggula granitoid pluton. Table S5: Zircon fission-track data of samples from the Tanggula granitoid pluton. Table S6: Apatite fission-track data of samples from the Tanggula granitoid pluton. Table S7: Single-grain zircon (U-Th)He data of samples from the Tanggula granitoid pluton. </p>
Cell-Penetrating Peptides as Vehicles for Delivery of Therapeutic Nucleic Acids. Mechanisms and Application in Medicine
Authors: Timotievich Ekaterina D. , Shilovskiy Igor P. , Khaitov Musa R. 
Published: November 2023

Abstract
Currently, nucleic acid therapeutics are actively developed for the treatment and prophylactic of metabolic disorders and oncological, inflammatory, and infectious diseases. A growing number of approved nucleic acid-based drugs evidences a high potential of gene therapy in medicine. Therapeutic nucleic acids act in the cytoplasm, which makes the plasma membrane the main barrier for the penetration of nucleic acid-based drugs into the cell and requires development of special vehicles for their intracellular delivery. The optimal carrier should not only facilitate internalization of nucleic acids, but also exhibit no toxic effects, ensure stabilization of the cargo molecules, and be suitable for a large-scale and low-cost production. Cell-penetrating peptides (CPPs), which match all these requirements, were found to be efficient and low-toxic carriers of nucleic acids. CPPs are typically basic peptides with a positive charge at physiological pH that can form nanostructures with negatively charged nucleic acids. The prospects of CPPs as vehicles for the delivery of therapeutic nucleic acids have been demonstrated in numerous preclinical studies. Some CPP-based drugs had successfully passed clinical trials and were implemented into medical practice. In this review, we described different types of therapeutic nucleic acids and summarized the data on the use of CPPs for their intracellular delivery, as well as discussed, the mechanisms of CPP uptake by the cells, as understanding of these mechanisms can significantly accelerate the development of new gene therapy approaches.
Determinants of government spending on primary healthcare: a global data analysis
Authors: Erlangga Darius , Powell-Jackson Timothy , Balabanova Dina , Hanson Kara 
Published: November 2023

In 2018 global leaders renewed their political commitment to primary healthcare (PHC) ratifying the Declaration of Astana emphasising the importance of building a sustainable PHC system based on accessible and affordable delivery models strengthened by community empowerment. Yet, PHC often remains underfunded, of poor quality, unreliable and not accountable to users which further deprives PHC of funding. This paper analyses the determinants of PHC expenditure in 102 countries, and quantitatively tests the influence of a set of economic, social and political determinants of government expenditure on PHC. The analysis is focused on the determinants of PHC funding from government sources as the government is in a position to make decisions in relation to this expenditure as opposed to out-of-pocket spending which is not in their direct control. Multivariate regression analysis was done to determine statistically significant predictors.Our analysis found that some economic factors—namely Gross Domestic Product (GDP) per capita, government commitment to health and tax revenue raising capacity—were strongly associated with per capita government spending on PHC. We also found that control of corruption was strongly associated with the level of total spending on PHC, while voice and accountability were positively associated with greater government commitment to PHC as measured by government spending on PHC as a share of total government health spending.Our analysis takes a step towards understanding of the drivers of PHC expenditure beyond the level of national income. Some of these drivers may be beyond the remit of health policy decision makers and relate to broader governance arrangements and political forces in societies. Thus, efforts to prioritise PHC in the health agenda and increase PHC expenditure should recognise the constraints within the political landscapes and engage with a wide range of actors who influence decisions affecting the health sector.
‘What we lacked was the courage to take decisions that differed from the rest of the world’: expert perspectives on the role of evidence in COVID-19 policymaking in Iraq
Authors: Alshalah Ali , Douedari Yazan , Howard Natasha 
Published: November 2023

IntroductionIraq reported its first COVID-19 case on 24 February 2020 and formed a national committee and advisory committees to support its response. While global experts have suggested that the COVID-19 pandemic provided an exceptional opportunity for advancing evidence-informed policymaking (EIPM), no research has examined this in Iraq. Therefore, this study aimed to examine evidence use in COVID-19 policymaking in Iraq.MethodsThis qualitative study employed semi-structured interviews with 20 Iraqi policymakers and researchers. Data were analysed thematically in Arabic using inductive coding.FindingsParticipants described COVID-19 policy in Iraq as based on research conducted in other countries, with poor access and quality of routine data and lack of national research priorities and academic freedom as barriers to national research production. Most researchers influenced policy individually, with universities and other research bodies not seen as contributing to policy development. Public non-compliance could be traced to mistrust in both political and healthcare systems and became particularly problematic during the pandemic. Proposed strategies to increase national research production included dedicated funding, establishing communication and collaboration for research priority setting, and protection of academic freedom.ConclusionSociopolitical and economic realities in Iraq were unsupportive of national or subnational evidence generation even before the COVID-19 pandemic, and government relied on international evidence and policy transfer rather than contextually informed EIPM. Strengthening evidence-informed infectious disease policymaking and policy transfer would thus require governmental focus on improving the quality and relevance of Iraqi research, engagement between researchers and policymakers, and processes of evidence use and policy transfer.
Add-on pramipexole for anhedonic depression: study protocol for a randomised controlled trial and open-label follow-up in Lund, Sweden
Authors: Lindahl Jesper , Asp Marie , Ståhl Darya , Tjernberg Johanna , Eklund Moa , Björkstrand Johannes , van Westen Danielle , Jensen Jimmy , Månsson Kristoffer , Tornberg Åsa , Svensson Martina , Deierborg Tomas , Ventorp Filip , Lindqvist Daniel 
Published: November 2023

IntroductionMany depressed patients do not achieve remission with available treatments. Anhedonia is a common residual symptom associated with treatment resistance as well as low function and quality of life. There are currently no specific and effective treatments for anhedonia. Some trials have shown that dopamine agonist pramipexole is efficacious for treating depression, but more data is needed before it could become ready for clinical prime time. Given its mechanism of action, pramipexole might be a useful treatment for a depression subtype characterised by significant anhedonia and lack of motivation—symptoms associated with dopaminergic hypofunction. We recently showed, in an open-label pilot study, that add-on pramipexole is a feasible treatment for depression with significant anhedonia, and that pramipexole increases reward-related activity in the ventral striatum. We will now confirm or refute these preliminary results in a randomised controlled trial (RCT) and an open-label follow-up study.Methods and analysisEighty patients with major depression (bipolar or unipolar) or dysthymia and significant anhedonia according to the Snaith Hamilton Pleasure Scale (SHAPS) are randomised to either add-on pramipexole or placebo for 9 weeks. Change in anhedonia symptoms per the SHAPS is the primary outcome, and secondary outcomes include change in core depressive symptoms, apathy, sleep problems, life quality, anxiety and side effects. Accelerometers are used to assess treatment-associated changes in physical activity and sleep patterns. Blood and brain biomarkers are investigated as treatment predictors and to establish target engagement. After the RCT phase, patients continue with open-label treatment in a 6-month follow-up study aiming to assess long-term efficacy and tolerability of pramipexole.Ethics and disseminationThe study has been approved by the Swedish Ethical Review Authority and the Swedish Medical Products Agency. The study is externally monitored according to Good Clinical Practice guidelines. Results will be disseminated via conference presentations and peer-reviewed publications.Trial registration numberNCT05355337andNCT05825235.
Clinical and Immunologic Features of Germline Pathogenic Variant–Positive Patients with Melanoma
Authors: Shen Alan , Arbesman Michelle , Lodha Roshan , Rayman Patricia , Bungo Brandon , Ni Ying , Chan Timothy , Gastman Brian , Ko Jennifer , Diaz-Montero C. Marcela , Arbesman Joshua , Funchain Pauline 
Published: November 2023

Abstract

Purpose:
Malignant melanoma represents the most lethal skin cancer with germline predispositions thought to comprise 10% to 15% of all melanoma cases. No studies to date examine the immunologic features that may differentiate survival differences between germline pathogenic variant (gPV)–positive patients with melanoma from gPV-negative patients with melanoma.

Experimental Design:
Adult patients with melanoma and clinical characteristics suggesting hereditary predisposition to cancer were prospectively recruited to undergo germline testing and flow cytometric analysis of peripheral immune suppressor cells.

Results:
In this cohort, gPV-positive patients (n = 72) had a significantly improved melanoma-specific survival (MSS) compared with gPV-negative patients (n = 411; HRadj, 0.32; 95% CI, 0.13–0.82; P = 0.01). These survival improvements among gPV-positive patients were most apparent among cutaneous melanoma subtypes (HRadj, 0.12; 95% CI, 0.016–0.86; P = 0.03) and numerically improved in later-stage (IIB–IV) patients (HRadj, 0.34; 95% CI, 0.10–1.11; P = 0.06). Further, gPV-positive patients had a significantly lower level of total circulating PMN-MDSC compared with gPV-negative patients (P = 0.01), which was most apparent in those diagnosed with later stages (IIB–IV) of melanoma (P = 0.009). Finally, a significant upregulation of inflammatory transcriptome signatures in later-stage gPV-positive patients (n = 21) was observed in comparison with gPV-negative patients (n = 173) in the cutaneous melanoma cohort (SKCM) of The Cancer Genome Atlas (TCGA).

Conclusions:
gPV-positive patients with melanoma exhibit improved MSS in addition to reduced peripheral PMN-MDSC and an enhanced inflammatory microenvironment.
Glucocorticoid Receptor (GR) Activation Is Associated with Increased cAMP/PKA Signaling in Castration-Resistant Prostate Cancer
Authors: Bennett Lynda , Jaiswal Praveen Kumar , Harkless Ryan V. , Long Tiha M. , Gao Ning , Vandenburg Brianna , Selman Phillip , Durdana Ishrat , Lastra Ricardo R. , Vander Griend Donald , Adelaiye-Ogala Remi , Szmulewitz Russell Z. , Conzen Suzanne D. 
Published: November 2023

Abstract
In castration-resistant prostate cancer (CRPC), increased glucocorticoid receptor (GR) expression and ensuing transcriptional activity have been proposed as an oncogenic “bypass” mechanism in response to androgen receptor (AR) signaling inhibition (ARSi). Here, we report that GR transcriptional activity acquired following ARSi is associated with the upregulation of cyclic adenosine monophosphate (cAMP)-associated gene expression pathways in both model systems and metastatic prostate cancer patient samples. In the context of ARSi, the expression of GR-mediated genes encoding cAMP signaling pathway-associated proteins can be inhibited by treatment with selective GR modulators (SGRMs). For example, in the context of ARSi, we found that GR activation resulted in upregulation of protein kinase inhibitor beta (PKIB) mRNA and protein levels, leading to nuclear accumulation of the cAMP-dependent protein kinase A catalytic subunit (PKA-c). Increased PKA-c, in turn, is associated with increased cAMP response element-binding protein phosphorylation and activity. Furthermore, enzalutamide and SGRM combination therapy in mice bearing CRPC xenografts delayed CRPC progression compared with enzalutamide therapy alone, and reduced tumor PKIB mRNA expression. Supporting the clinical importance of GR/PKA signaling activation in CRPC, we found a significant enrichment of both cAMP pathway signaling-associated gene expression and high NR3C1 (GR) activity in patient-derived xenograft models and metastatic human CRPC samples. These findings suggest a novel mechanism linking CRPC-induced GR transcriptional activity with increased cAMP signaling in AR-antagonized CRPC. Furthermore, our findings suggest that GR-specific modulation in addition to AR antagonism may delay GR+ CRPC time to recurrence, at least in part, by inhibiting tumor cAMP/PKA pathways.
Upholding Banker’s Duty of Confidentiality in Tanzania: an Examination of Legislative and Judicial Responses
Authors: Temu Goodluck 
Published: November 2023

Abstract
Trust and confidence are the foundations of a banker-customer relationship. As a result, any information customers submit to their bankers is expected to be kept confidential. This expectation can only be met if the relevant legislative frameworks are in place to ensure that bankers are held accountable for their confidentiality agreements. While there is legislation in place to protect the privacy of customer information in Tanzania, a growing number of laws, notably those dealing with crime prevention and control, have been enacted, with the consequence of undermining bankers’ confidentiality obligations. Therefore, this article examines how recent legislative and judicial developments have addressed the confidentiality obligations imposed on bankers. In general, it has been observed and established that the protection of customers’ information provided by banking laws is usually degraded by other laws, particularly those pertaining to crime prevention, hence weakening banker’s duty of confidentiality.
Regional Characteristics of Attribution Risk on the Record-High-Temperature Event of 2022 Rainy Season in Japan
Authors: Ito Rui , Imada Yukiko , Kawase Hiroaki 
Published: November 2023

Abstract
The attribution of 2022’s high temperatures in Japan to human-induced climate change exhibits significant regional variability, with FARs of 0.33–1, influenced by large-scale wind changes and regional topography.