bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomics and metabolomics analyses of camptothecin-producing
Aspergillus terreus
reveal the integration of PH domain-containing proteins and peptidylprolyl cis/trans isomerase in restoring the camptothecin biosynthesis
Authors: Rady Amgad M. , El-Sayed Ashraf S. A. , El-Baz Ashraf F. , Abdel-Fattah Ghada G. , Magdeldin Sameh , Ahmed Eman , Osama Aya , Hassanein Sameh E. , Saed Hend , Yassin Marwa 
Published: October 2023

ABSTRACT

Attenuating the expression of fungal camptothecin biosynthetic genes with subculturing is the challenge that halts their further implementation. The camptothecin productivity of the subcultured
Aspergillus terreus
has been restored upon addition of
Ficus elastica
indigenous microbiome; however, the identity of triggering signals of
A. terreus
camptothecin biosynthesis remains ambiguous. In this study, differential proteomics and metabolomics analyses were implemented to unravel the differentially abundant proteins and metabolites associated with the weakening/restoration of the biosynthetic machinery of camptothecin by
A. terreus
. The functional proteins, namely, ribosomal proteins, ATP, metal ion, and GTP binding proteins, were abolished by the seventh culture of
A. terreus
; however, the expression of these proteins was completely restored upon addition of
F. elastica
microbiome. Among the proteins of highly altered abundance, Pleckstrin homology (PH) domain-containing protein, peptidylprolyl
cis
/
trans
isomerase, 60S ribosomal protein, and So-Cu domain-containing proteins were significantly decreased with subculturing of
A. terreus
and strikingly restored upon addition of
F. elastica
microbiome. The metabolites 5,7-dihydroxy-2-(4-hydroxyphenyl)-3,6-dimethoxy-4H-chromen and glutaric acid of
A. terreus
were significantly decreased with subculturing and completely restored upon addition of
F. elastica
microbiome. The most differentially abundant metabolites were involved in glycolysis, TCA cycle, mevalonate pathway, terpenoids and shikimate synthesis, and ultimately with camptothecin biosynthesis. Thus, overexpression of PH domain-containing protein and peptidylprolyl
cis
/
trans
isomerase could be a new avenue for a metabolically stable camptothecin producing
A. terreus
.

IMPORTANCE

Decreasing the camptothecin productivity by fungi with storage and subculturing is the challenge that halts their further implementation to be an industrial platform for camptothecin (CPT) production. The highest differentially abundant proteins were Pleckstrin homology (PH) domain-containing proteins and Peptidyl-prolyl
cis
/
trans
isomerase that fluctuated with the subculturing of
A. terreus
with a remarkable relation to CPT biosynthesis and restored with addition of
F. elastica
microbiome.
CCDC66
mutations are associated with high myopia through affected cell mitosis
Authors: Chen Xiaozhen , Tong Ping , Jiang Ying , Cheng Zhe , Zang Liyu , Yang Zhikuan , Lan Weizhong , Xia Kun , Hu Zhengmao , Tian Qi 
Published: October 2023

Background
High myopia (HM) refers to an eye refractive error exceeding −5.00 D, significantly elevating blindness risk. The underlying mechanism of HM remains elusive. Given the extensive genetic heterogeneity and vast genetic base opacity, it is imperative to identify more causative genes and explore their pathogenic roles in HM.

Methods
We employed exome sequencing to pinpoint the causal gene in an HM family. Sanger sequencing was used to confirm and analyse the gene mutations in this family and 200 sporadic HM cases. Single-cell RNA sequencing was conducted to evaluate the gene’s expression patterns in developing human and mouse retinas. The CRISPR/Cas9 system facilitated the gene knockout cells, aiding in the exploration of the gene’s function and its mutations. Immunofluorescent staining and immunoblot techniques were applied to monitor the functional shifts of the gene mutations at the cellular level.

Results

A suspected nonsense mutation (c.C172T, p.Q58X) in
CCDC66
was found to be co-segregated with the HM phenotype in the family. Additionally, six other rare variants were identified among the 200 sporadic patients.
CCDC66
was consistently expressed in the embryonic retinas of both humans and mice. Notably, in CCDC66-deficient HEK293 cells, there was a decline in cell proliferation, microtube polymerisation rate and ace-tubulin level. Furthermore, the mutated CCDC66 failed to synchronise with the tubulin system during Hela cell mitosis, unlike its wild type counterpart.

Conclusions

Our research indicates that the
CCDC66
variant c.C172T is associated with HM. A deficiency in CCDC66 might disrupt cell proliferation by influencing the mitotic process during retinal growth, leading to HM.
High-intensity interval training attenuates impairment in regulatory protein machinery of mitochondrial quality control in skeletal muscle of diet-induced obese mice
Authors: Tincknell James B. , Kugler Benjamin A. , Spicuzza Haley , Berger Nicolas , Yan Huimin , You Tongjian , Zou Kai 
Published: October 2023

Mitochondrial quality control processes are essential in governing mitochondrial integrity and function. The purpose of the study was to examine the effects of 10 weeks of high-intensity interval training (HIIT) on the regulatory protein machinery of skeletal muscle mitochondrial quality control and whole-body glucose homeostasis in diet-induced obese mice. Male C57BL/6 mice were assigned to low-fat diet (LFD) or high-fat diet (HFD) group. After 10 weeks, HFD-fed mice were divided into sedentary and HIIT (HFD + HIIT) groups for another 10 weeks ( n = 9/group). Graded exercise test, glucose and insulin tolerance tests, mitochondrial respiration, and protein markers of mitochondrial quality control processes were determined. HFD-fed mice exhibited lower ADP-stimulated mitochondrial respiration ( p < 0.05). However, 10 weeks of HIIT prevented this impairment ( p < 0.05). Importantly, the ratio of Drp1(Ser616) over Drp1(Ser637) phosphorylation, an indicator of mitochondrial fission, was significantly higher in HFD-fed mice ( p < 0.05), but such increase was attenuated in HFD-HIIT compared to HFD (−35.7%, p < 0.05). Regarding autophagy, skeletal muscle p62 content was lower in the HFD group than the LFD group (−35.1%, p < 0.05); however, such reduction was disappeared in the HFD + HIIT group. In addition, LC3B II/I ratio was higher in the HFD group than the LFD group (15.5%, p < 0.05) but was ameliorated in the HFD + HIIT group (−29.9%, p < 0.05). Overall, our study demonstrated that 10 weeks of HIIT was effective in improving skeletal muscle mitochondrial respiration and the regulatory protein machinery of mitochondrial quality control in diet-induced obese mice through the alterations of mitochondrial fission protein Drp1 phosphorylations and p62/LC3B-mediated regulatory machinery of autophagy.
The July 1996 Saguenay Flood: geotechnical aspects
Authors: Leroueil Serge , Bouchard Régis , Demers Denis , Perret Didier 
Published: October 2023

Extreme rainfall occurred in July 1996 over the Saguenay Region, some 200 km north of Quebec City. With about 1000 landslides, seven damaged dams, one dike failure, washed out road sections, tens of bridges damaged or destroyed, 1700 properties destroyed or damaged and several casualties, this event was one of the most important natural disasters in Canada. Detailed geotechnical investigations permitted better understanding of the soils involved, mainly sensitive clays and their superficial crust, including their behaviour in landslides, the erosion processes, impacts on infrastructure and sediment deposition.
On the two-loop BSM corrections to $$h\longrightarrow \gamma \gamma $$ in the aligned THDM
Authors: Degrassi Giuseppe , Slavich Pietro 
Published: October 2023

AbstractWe compute the two-loop BSM contributions to the $$h\longrightarrow \gamma \gamma $$

h
⟶
γ
γ

decay width in the aligned THDM. We adopt the simplifying assumptions of vanishing EW gauge couplings and vanishing mass of the SM-like Higgs boson, which allow us to exploit a low-energy theorem connecting the $$h\gamma \gamma $$

h
γ
γ

amplitude to the derivative of the photon self-energy w.r.t. the Higgs field. We briefly discuss the numerical impact of the newly-computed contributions, showing that they may be required for a precise determination of $$\Gamma [h\rightarrow \gamma \gamma ]$$

Γ
[
h
→
γ
γ
]

in scenarios where the quartic Higgs couplings are large.
Soft syndrome iterative decoding of quantum LDPC codes and hardware architectures
Authors: Raveendran Nithin , Valls Javier , Pradhan Asit Kumar , Rengaswamy Narayanan , Garcia-Herrero Francisco , Vasić Bane 
Published: October 2023

AbstractIn practical quantum error correction implementations, the measurement of syndrome information is an unreliable step—typically modeled as a binary measurement outcome flipped with some probability. However, the measured syndrome is in fact a discretized value of the continuous voltage or current values obtained in the physical implementation of the syndrome extraction. In this paper, we use this “soft” or analog information to benefit iterative decoders for decoding quantum low-density parity-check (QLDPC) codes. Syndrome-based iterative belief propagation decoders are modified to utilize the soft syndrome to correct both data and syndrome errors simultaneously. We demonstrate the advantages of the proposed scheme not only in terms of comparison of thresholds and logical error rates for quasi-cyclic lifted-product QLDPC code families but also with faster convergence of iterative decoders. Additionally, we derive hardware (FPGA) architectures of these soft syndrome decoders and obtain similar performance in terms of error correction to the ideal models even with reduced precision in the soft information. The total latency of the hardware architectures is about 600 ns (for the QLDPC codes considered) in a 20 nm CMOS process FPGA device, and the area overhead is almost constant—less than 50% compared to min-sum decoders with noisy syndromes.
Role of cAMP in Cardiomyocyte Viability: Beneficial or Detrimental?
Authors: Zhang Yishuai , Chen Si , Luo Lingfeng , Greenly Sarah , Shi Hangchuan , Xu Jasmine Jiayuan , Yan Chen 
Published: October 2023

BACKGROUND:
3′, 5′-cyclic AMP (cAMP) regulates numerous cardiac functions. Various hormones and neurotransmitters elevate intracellular cAMP (i[cAMP]) in cardiomyocytes through activating GsPCRs (stimulatory-G-protein-coupled-receptors) and membrane-bound ACs (adenylyl cyclases). Increasing evidence has indicated that stimulating different GsPCRs and ACs exhibits distinct, even opposite effects, on cardiomyocyte viability. However, the underlying mechanisms are not fully understood.

METHODS:
We used molecular and pharmacological approaches to investigate how different GsPCR/cAMP signaling differentially regulate cardiomyocyte viability with in vitro, ex vivo, and in vivo models.

RESULTS:

For prodeath GsPCRs, we explored β1AR (beta1-adrenergic receptor) and H2R (histamine-H2-receptor). We found that their prodeath effects were similarly dependent on AC5 activation, ATP release to the extracellular space via PANX1 (pannexin-1) channel, and extracellular ATP (e[ATP])-mediated signaling involving in P2X7R (P2X purinoceptor 7) and CaMKII (Ca
2+
/calmodulin-dependent protein kinase II). PANX1 phosphorylation at Serine 206 by cAMP-dependent-PKA (protein-kinase-A) promoted PANX1 activation, which was critical in β1AR- or H2R-induced cardiomyocyte death in vitro and in vivo. β1AR or H2R was localized proximately to PANX1, which permits ATP release. For prosurvival GsPCRs, we explored adenosine-A2-receptor (A2R), CGRPR (calcitonin-gene-related-peptide-receptor), and RXFP1 (relaxin-family peptide-receptor 1). Their prosurvival effects were dependent on AC6 activation, cAMP efflux via MRP4 (multidrug resistance protein 4), extracellular cAMP metabolism to adenosine (e[cAMP]-to-e[ADO]), and e[ADO]-mediated signaling. A2R, CGRPR, or RXFP1 was localized proximately to MRP4, which enables cAMP efflux. Interestingly, exogenously increasing e[cAMP] levels by membrane-impermeable cAMP protected against cardiomyocyte death in vitro and in ex vivo and in vivo mouse hearts with ischemia-reperfusion injuries.

CONCLUSIONS:
Our findings indicate that the functional diversity of different GsPCRs in cardiomyocyte viability could be achieved by their ability to form unique signaling complexes (signalosomes) that determine the fate of cAMP: either stimulate ATP release by activating PKA or directly efflux to be e[cAMP].
Performance of Thrombectomy-Capable, Comprehensive, and Primary Stroke Centers in Reperfusion Therapies for Acute Ischemic Stroke: Report From the Get With The Guidelines–Stroke Registry
Authors: Raychev Radoslav , Sun Jie-Lena , Schwamm Lee , Smith Eric E. , Fonarow Gregg C. , Messé Steven R. , Xian Ying , Chiswell Karen , Blanco Rosalia , Mac Grory Brian , Saver Jeffrey L. 
Published: October 2023

BACKGROUND:
The thrombectomy-capable stroke center (TSC) is a recently introduced intermediate tier of accreditation for hospitals at which patients with acute ischemic stroke receive care. The comparative quality and clinical outcomes of reperfusion therapies at TSCs, primary stroke centers (PSCs), and comprehensive stroke centers (CSCs) have not been well delineated.

METHODS:
We conducted a retrospective, observational, cohort study from 2018 to 2020 that included patients with acute ischemic stroke who received endovascular thrombectomy (EVT) and intravenous thrombolysis reperfusion therapies at CSCs, TSCs, or PSCs. Participants were recruited from Get With The Guidelines–Stroke registry. Study end points included timeliness of intravenous thrombolysis and EVT, successful reperfusion, discharge destination, discharge mortality, and functional independence at discharge.

RESULTS:
Among 84 903 patients, 48 682 received EVT, of whom 73% were treated at CSCs, 22% at PSCs, and 4% at TSCs. The median annual EVT volume was 76 for CSCs, 55 for TSCs, and 32 for PSCs. Patient differences by center status included higher National Institutes of Health Stroke Scale score, longer onset-to-arrival time, and higher transfer-in rates for CSCs, TSCs, and PSCs, respectively. In adjusted analyses, the likelihood of achieving the goal door-to-needle time was higher in CSCs compared with PSCs (odds ratio [OR], 1.39 [95% CI, 1.17–1.66]) and in TSCs compared with PSCs (OR, 1.45 [95% CI, 1.08–1.96]). Likewise, the odds of achieving the goal door-to-puncture time were higher in CSCs compared with PSCs (OR, 1.58 [95% CI, 1.13–2.21]). CSCs and TSCs also demonstrated better clinical efficacy outcomes compared with PSCs. The odds of discharge to home or rehabilitation were higher in CSCs compared with PSCs (OR, 1.18 [95% CI, 1.06–1.31]), whereas the odds of in-hospital mortality or discharge to hospice were lower in both CSCs compared with PSCs (OR, 0.87 [95% CI, 0.81–0.94]) and TSCs compared with PSCs (OR, 0.86 [95% CI, 0.75–0.98]). There were no significant differences in any of the quality-of-care metrics and clinical outcomes between TSCs and CSCs.

CONCLUSIONS:
In this study representing national US practice, CSCs and TSCs exceeded PSCs in key quality-of-care reperfusion metrics and outcomes, whereas TSCs and CSCs demonstrated a similar performance. With more than one-fifth of all EVT procedures during the study period conducted at PSCs, it may be desirable to explore national initiatives aimed at facilitating the elevation of eligible PSCs to a higher certification status.
Arterial Stiffness and Cardiorespiratory Fitness Impairment in the Community
Authors: Nayor Matthew , Gajjar Priya , Miller Patricia , Murthy Venkatesh L. , Shah Ravi V. , Houstis Nicholas E. , Velagaleti Raghava S. , Larson Martin G. , Vasan Ramachandran S. , Lewis Gregory D. , Mitchell Gary F. 
Published: October 2023

Background
During exercise, a healthy arterial system facilitates increased blood flow and distributes it effectively to essential organs. Accordingly, we sought to understand how arterial stiffening might impair cardiorespiratory fitness in community‐dwelling individuals.

Methods and Results

Arterial tonometry and maximum effort cardiopulmonary exercise testing were performed on Framingham Heart Study participants (N=2898, age 54±9 years, 53% women, body mass index 28.1±5.3 kg/m
2
). We related 5 arterial stiffness measures (carotid‐femoral pulse wave velocity [CFPWV]: a measure of aortic wall stiffness; central pulse pressure, forward wave amplitude, characteristic impedance: measures of pressure pulsatility; and augmentation index: a measure of relative wave reflection) to multidimensional exercise responses using linear models adjusted for age, sex, resting heart rate, habitual physical activity, and clinical risk factors. Greater CFPWV, augmentation index, and characteristic impedance were associated with lower peak oxygen uptake (VO
2
; all
P
<0.0001). We observed consistency of associations of CFPWV with peak oxygen uptake across age, sex, and cardiovascular risk profile (interaction
P
>0.05). However, the CFPWV‐peak oxygen uptake relation was attenuated in individuals with obesity (
P
=0.002 for obesity*CFPWV interaction). Higher CPFWV, augmentation index, and characteristic impedance were also related to cardiopulmonary exercise testing measures reflecting adverse O
2
kinetics and lower stroke volume and peripheral O
2
extraction but not to ventilatory efficiency, a prognostic measure of right ventricular‐pulmonary vascular performance.

Conclusions
Our findings delineate relations of arterial stiffness and cardiorespiratory fitness in community‐dwelling individuals. Future studies are warranted to evaluate whether the physiological measures implicated here may represent potential targets for improving cardiorespiratory fitness in the general population.
Uniquely Creative Together
Authors: Redfern Lindi , Finestone Michelle 
Published: October 2023

Abstract
This paper discusses silent group Sandplay (SP) with early adolescents in circumstances of deprivation, neglect and trauma. SP offered in multiple layers of temenos in a children’s home environment provided a conducive context for inner processing. Considered from a Jungian perspective, SP revealed inner processing at work. Initial portrayals included threats, conflict and chaos, the need for protection and containment and revealed vulnerability. Later SP images and processes depicted progression and regression, uniquely creative together as well as containment and activation of movement. Silent group SP supported and facilitated transcendental and self encounters that included centring, integration, wholeness, numinous and newfound energy. The implications are potentially far-reaching in terms of the relative affordability, accessibility, efficiency and cultural suitability of this intervention that is not reliant on the verbal skills of the participants or the therapist and can be offered to several individuals simultaneously.
The Commercial Crisis in Makkah after the Prophet’s Hijra
Authors: Al Shuwaier Mohammed Abdullah 
Published: October 2023

Abstract
This article examines the economic effects of the Hijra of the Prophet Muhammad (pbuh) on the economy of Makkah until the conquest of Makkah in year ah 8/630 ce. Attention is given to the importance of commercial life in Makkan society from the fifth century ce, emphasizing the two mercantile journeys of the Makkan Quraysh to the north and the south, as well as the īlāf pacts between the Quraysh and the tribes whose lands their merchant caravans passed through. The important roles played by the tribes in facilitating Makkah commerce was studied, and examples are given of prominent Makkan merchants and Makkan markets before Islam. This is followed by a discussion of the reaction of Quraysh to the mission of the Prophet (pbuh), the Hijra, and the beginning and development of the commercial crisis in Makkah until the conquest of the city in ah 8/632 ce.
Efficacy and safety of probiotic-supplemented bismuth quadruple therapy for the treatment of Helicobacter pylori infection: a systematic review and meta-analysis
Authors: Yao Gaoyan , Fan Xiaoyuan , Lu Dewen 
Published: October 2023

Objective We performed a meta-analysis to determine whether the addition of probiotics to the bismuth quadruple therapy (BQT) for Helicobacter pylori would improve the incidence of eradication and reduce that of side effects. Methods Randomized controlled trials matching the inclusion criteria were collected from PubMed, Embase, Web of Science, and The Cochrane Central Register of Controlled Trials. A Mantel–Haenszel random-effects model was used to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs) for the incidences of eradication rate, side effects as a whole, diarrhea, and other side effects. Results Ten studies were selected for inclusion in the meta-analysis. The pooled RRs for the eradication rates in intention-to-treat and per-protocol analyses of the probiotic group vs. the control group were 1.07 (95% CI: 1.02–1.11) and 1.04 (95% CI: 1.00–1.07), respectively. Probiotic supplementation reduced the incidences of side effects (RR 0.58, 95% CI: 0.37–0.91), diarrhea (RR 0.41, 95% CI: 0.25–0.67), and bitter taste (RR 0.63, 95% CI: 0.40–0.99). Conclusions The results of this meta-analysis support the use of probiotics in combination with BQT in the clinical management of patients with H. pylori infection.
Potential diagnostic value of multiple indicators combined with total prostate-specific antigen in prostate cancer
Authors: Zhang Qingxu , Li Haodong , Song Zhiguo , Kong Shaopeng , Zhao Sitao , Fan Siqi , Qin Fei , Ma Jianguo 
Published: October 2023

Objective We aimed to investigate the diagnostic value of different laboratory indicators in combination with total prostate-specific antigen (TPSA) for prostate cancer (PCa). Methods In this retrospective study, we selected 291 patients who underwent prostate biopsy. Patients were divided into the benign prostatic hyperplasia group and the PCa group. In both groups, patients were again divided into a group with TPSA 4.0–10.0 ng/mL and a group with TPSA >10.0 ng/mL. Clinical data including age, pre-puncture TPSA, free prostate-specific antigen (FPSA), and prostate volume (PV) were collected from all patients. We calculated the metrics PSA/PV (prostate-specific antigen density, PSAD), age/PV (AVR), age × PV/TPSA (PSA-AV), and (FPSA/TPSA)/PSAD [(F/T)/PSAD]). We plotted receiver operating characteristic (ROC) curves and calculated the area under the ROC curve (AUC). Results We found statistically significant differences in PV, PSAD, AVR, PSA-AV, and (F/T) PSAD for patients with TPSA 4.0–10.0 ng/mL and TPSA >10 ng/mL. We further plotted the ROC of individual or combined indices in different subgroups and calculated the AUC. We found that the diagnostic efficacy of the combined indices was higher with TPSA >10 ng/mL. Conclusion The combination of TPSA with multiple indicators may improve diagnostic accuracy for PCa.