bluuebunny/crossref_metadata_2025 huggingface dataset:
Bottlenose dolphin temporary threshold shift following exposure to 10-ms impulses centered at 8 kHz
Authors: Mulsow Jason , Schlundt Carolyn E. , Strahan Madelyn G. , Finneran James. J.
Published: August 2023

Studies of marine mammal temporary threshold shift (TTS) from impulsive sources have typically produced small TTS magnitudes, likely due to much of the energy in tested sources lying below the subjects' range of best hearing. In this study of dolphin TTS, 10-ms impulses centered at 8 kHz were used with the goal of inducing larger magnitudes of TTS and assessing the time course of hearing recovery. Most impulses had sound pressure levels of 175–180 dB re 1 μPa, while inter-pulse interval (IPI) and total number of impulses were varied. Dolphin TTS increased with increasing cumulative sound exposure level (SEL) and there was no apparent effect of IPI for exposures with equal SEL. The lowest TTS onset was 184 dB re 1 μPa2s, although early exposures with 20-s IPI and cumulative SEL of 182–183 dB re 1 μPa2s produced respective TTS of 35 and 16 dB in two dolphins. Continued testing with higher SELs up to 191 dB re 1 μPa2s in one of those dolphins, however, failed to result in TTS greater than 14 dB. Recovery rates were similar to those from other studies with non-impulsive sources and depended on the magnitude of the initial TTS.
Pathway-specific inputs to the superior colliculus support flexible responses to visual threat
Authors: Li Chen , Kühn Norma K. , Alkislar Ilayda , Sans-Dublanc Arnau , Zemmouri Firdaouss , Paesmans Soraya , Calzoni Alex , Ooms Frédérique , Reinhard Katja , Farrow Karl
Published: August 2023

Behavioral flexibility requires directing feedforward sensory information to appropriate targets. In the superior colliculus, divergent outputs orchestrate different responses to visual threats, but the circuit organization enabling the flexible routing of sensory information remains unknown. To determine this structure, we focused on inhibitory projection (Gad2) neurons. Trans-synaptic tracing and neuronal recordings revealed that Gad2 neurons projecting to the lateral geniculate nucleus (LGN) and the parabigeminal nucleus (PBG) form two separate populations, each receiving a different set of non-retinal inputs. Inhibiting the LGN- or PBG-projecting Gad2 neurons resulted in opposing effects on behavior; increasing freezing or escape probability to visual looming, respectively. Optogenetic activation of selected inputs to the LGN- and PBG-projecting Gad2 cells predictably regulated responses to visual threat. These data suggest that projection-specific sampling of brain-wide inputs provides a circuit design principle that enables visual inputs to be selectively routed to produce context-specific behavior.
The neural code for “face cells” is not face-specific
Authors: Vinken Kasper , Prince Jacob S. , Konkle Talia , Livingstone Margaret S.
Published: August 2023

Face cells are neurons that respond more to faces than to non-face objects. They are found in clusters in the inferotemporal cortex, thought to process faces specifically, and, hence, studied using faces almost exclusively. Analyzing neural responses in and around macaque face patches to hundreds of objects, we found graded response profiles for non-face objects that predicted the degree of face selectivity and provided information on face-cell tuning beyond that from actual faces. This relationship between non-face and face responses was not predicted by color and simple shape properties but by information encoded in deep neural networks trained on general objects rather than face classification. These findings contradict the long-standing assumption that face versus non-face selectivity emerges from face-specific features and challenge the practice of focusing on only the most effective stimulus. They provide evidence instead that category-selective neurons are best understood by their tuning directions in a domain-general object space.
Inhibiting sorting nexin 10 promotes mucosal healing through SREBP2-mediated stemness restoration of intestinal stem cells
Authors: Bao Weilian , You Yan , Ni Jiahui , Hou Hui , Lyu Jiaren , Feng Guize , Wang Yirui , You Keyuan , Zhang Sulin , Zhang Lijie , Cao Xinyue , Wang Xu , Li Haidong , Li Hong , Xu Jiake , Liu Chenying , Luo Xiaomin , Du Peng , Chen Daofeng , Shen Xiaoyan
Published: August 2023

Intestinal stem cell (ISC) is a promising therapeutic target for inflammatory bowel disease. Cholesterol availability is critical for ISC stemness. Low plasma cholesterol is a typical feature of Crohn’s disease (CD); however, its impact on mucosal healing remains unclear. Here, we identified an essential role of sorting nexin 10 (SNX10) in maintaining the stemness of ISCs. SNX10 expression in intestinal tissues positively correlates with the severity of human CD and mouse colitis. Conditional SNX10 knockout in intestinal epithelial cells or ISCs promotes intestinal mucosal repair by maintaining the ISC population associated with increased intracellular cholesterol synthesis. Disassociation of ERLIN2 with SCAP by SNX10 deletion enhances the activation of SREBP2, resulting in increased cholesterol biosynthesis. DC-SX029, a small-molecule inhibitor of SNX10, was used to verify the druggable potential of SNX10 for the treatment of patients with CD. Our study provides a strategy for mucosal healing through SREBP2-mediated stemness restoration of ISCs.
Serine protease 35 regulates the fibroblast matrisome in response to hyperosmotic stress
Authors: Sänger Catharina S. , Cernakova Martina , Wietecha Mateusz S. , Garau Paganella Lorenza , Labouesse Céline , Dudaryeva Oksana Y. , Roubaty Carole , Stumpe Michael , Mazza Edoardo , Tibbitt Mark W. , Dengjel Jörn , Werner Sabine
Published: August 2023

Hyperosmotic stress occurs in several diseases, but its long-term effects are largely unknown. We used sorbitol-treated human fibroblasts in 3D culture to study the consequences of hyperosmotic stress in the skin. Sorbitol regulated many genes, which help cells cope with the stress condition. The most robustly regulated gene encodes serine protease 35 (PRSS35). Its regulation by hyperosmotic stress was dependent on the kinases p38 and JNK and the transcription factors NFAT5 and ATF2. We identified different collagens and collagen-associated proteins as putative PRSS35 binding partners. This is functionally important because PRSS35 affected the extracellular matrix proteome, which limited cell proliferation. The in vivo relevance of these findings is reflected by the coexpression of PRSS35 and its binding partners in human skin wounds, where hyperosmotic stress occurs as a consequence of excessive water loss. These results identify PRSS35 as a key regulator of the matrisome under hyperosmotic stress conditions.
Social media, extremism, and radicalization
Authors: Shaw Aaron
Published: August 2023

Fears that YouTube recommendations radicalize users are overblown, but social media still host and profit from dubious and extremist content.
The anti-CD40L monoclonal antibody AT-1501 promotes islet and kidney allograft survival and function in nonhuman primates
Authors: Anwar Imran J. , Berman Dora M. , DeLaura Isabel , Gao Qimeng , Willman Melissa A. , Miller Allison , Gill Alan , Gill Cindy , Perrin Steve , Ricordi Camillo , Ruiz Philip , Song Mingqing , Ladowski Joseph M. , Kirk Allan D. , Kenyon Norma S.
Published: August 2023

Prior studies of anti-CD40 ligand (CD40L)–based immunosuppression demonstrated effective prevention of islet and kidney allograft rejection in nonhuman primate models; however, clinical development was halted because of thromboembolic complications. An anti-CD40L-specific monoclonal antibody, AT-1501 (Tegoprubart), was engineered to minimize risk of thromboembolic complications by reducing binding to Fcγ receptors expressed on platelets while preserving binding to CD40L. AT-1501 was tested in both a cynomolgus macaque model of intrahepatic islet allotransplantation and a rhesus macaque model of kidney allotransplantation. AT-1501 monotherapy led to long-term graft survival in both islet and kidney transplant models, confirming its immunosuppressive potential. Furthermore, AT-1501–based regimens after islet transplant resulted in higher C-peptide, greater appetite leading to weight gain, and reduced occurrence of cytomegalovirus reactivation compared with conventional immunosuppression. These data support AT-1501 as a safe and effective agent to promote both islet and kidney allograft survival and function in nonhuman primate models, warranting further testing in clinical trials.
The mature N-termini of
Plasmodium
effector proteins confer specificity of export
Authors: Hasan Muhammad M. , Polino Alexander J. , Mukherjee Sumit , Vaupel Barbara , Goldberg Daniel E.
Published: August 2023

The intraerythrocytic malaria parasite
Plasmodium falciparum
exports hundreds of proteins into the host red blood cell (RBC). Most are targeted to the endoplasmic reticulum (ER) by a stretch of hydrophobic amino acids and cleaved further downstream at a conserved motif called the
Plasmodium
Export Element (PEXEL) by the ER protease plasmepsin V (PM V). The mature effectors then travel through the secretory pathway to the parasitophorous vacuole (PV) that surrounds the parasite. There, PEXEL proteins are somehow recognized as export-destined proteins, as opposed to PV-resident proteins, and are selectively translocated out into the RBC. The mature N-terminus appears to be important for export. There is conflicting data on whether PM V cleavage is needed for proper export or whether any means of generating the mature N-terminus would suffice. We replaced the PEXEL-containing N-terminal sequence of an exported GFP reporter with a signal peptide sequence and showed that precise cleavage by signal peptidase, generating the proper mature N-terminus, yields export competence. Expressing a construct with only the native ER targeting signal without the PM V cleavage site dramatically decreased the amount of a mature PEXEL reporter, indicating that the hydrophobic stretch lacks an efficient cleavage signal. Therefore, the PEXEL motif functions as a specialized signal cleavage site when appropriately located after an ER targeting sequence. Our data suggest that PM V cleavage and RBC export are two independent events for PEXEL proteins. We also tested and rejected the hypothesis that an alpha-helical mature N-terminus is necessary for export.

IMPORTANCE

Malaria parasites export hundreds of proteins to the cytoplasm of the host red blood cells for their survival. A five amino acid sequence, called the PEXEL motif, is conserved among many exported proteins and is thought to be a signal for export. However, the motif is cleaved inside the endoplasmic reticulum of the parasite, and mature proteins starting from the fourth PEXEL residue travel to the parasite periphery for export. We showed that the PEXEL motif is dispensable for export as long as identical mature proteins can be efficiently produced via alternative means in the ER. We also showed that the exported and non-exported proteins are differentiated at the parasite periphery based on their mature N-termini; however, any discernible export signal within that region remained cryptic. Our study resolves a longstanding paradox in PEXEL protein trafficking.
A
Toxoplasma gondii
lipoxygenase-like enzyme is necessary for virulence and changes localization associated with the host immune response
Authors: Ramírez-Flores Carlos J. , Erazo Flores Billy Joel , Tibabuzo Perdomo Andrés M. , Barnes Katie L. , Wilson Sarah K. , Mendoza Cavazos Carolina , Knoll Laura J.
Published: August 2023

While the asexual cycle of
Toxoplasma gondii
can occur in any warm-blooded animal, the sexual cycle is restricted to the feline intestine. We previously determined that because cats lack delta-6-desaturase activity in their intestines, they build up excess linoleic acid, which signals
T. gondii
to undergo sexual development. We hypothesized that
T. gondii
oxygenates linoleic acid to signal sexual development, so we examined the
T. gondii
genome for lipoxygenases-like enzymes (TgLOXL) enzymes. We identified seven TgLOXLs that were at least 100-fold more abundant in the cat intestinal versus the tissue culture tachyzoite stage. Parasites deleted in TgLOXL1 (TgΔLOXL1) had no significant growth differences in tissue culture fibroblast cells. Because the sexual development assay begins with brain cysts, we infected mice with TgΔLOXL1 and were surprised to find that TgΔLOXL1 had reduced virulence. The TgΔLOXL1 parasitemia was reduced by 3 d post-infection and largely cleared by 7 d post-infection. At 3 d post-infection, the cytokines interferon gamma (IFN-γ), IL-6, MCP-1, and TNF-α were significantly reduced in TgΔLOXL1-infected mice, which prompted us to examine TgΔLOXL1 in IFN-γ KO mice. We found that IFN-γ KO mice infected with TgΔLOXL1 succumbed to acute infection with the same kinetics as the parental and complemented strains, suggesting that TgLOXL1 plays a role in the IFN-γ signaling cascade. In tissue culture fibroblasts, TgLOXL1 was localized within the parasite, but in leukocytes from infected mice and activated macrophages, TgLOXL1 was localized within the host cytoplasm. These results suggest that TgLOXL1 changes localization in response to host immune activation.

IMPORTANCE

Lipoxygenases (LOXs) are enzymes that catalyze the deoxygenation of polyunsaturated fatty acids such as linoleic and arachidonic acid. These modifications create signaling molecules that are best characterized for modulating the immune response. Deletion of the first lipoxygenase-like enzyme characterized for
Toxoplasma gondii
(TgLOXL1) generated a less virulent strain, and infected mice showed a decreased immune response. This virulence defect was dependent on the mouse cytokine interferon gamma IFNγ. TgLOXL1 changes location from inside the parasite in tissue culture conditions to vesicular structures within the host immune cells during mouse infection. These results suggest that TgLOXL1 plays a role in the modification of the host immune response in mice.
A new hypothesis on BV etiology: dichotomous and crisscrossing categorization of complex versus simple on healthy versus BV vaginal microbiomes
Authors: Ma Zhanshan (Sam)
Published: August 2023

It has been estimated that bacterial vaginosis (BV) influences as many as one-third of women, but its etiology remains unclear. A traditionally held view is that dominance by
Lactobacillus
is the hallmark of a healthy vaginal microbiome (VM) and lack of dominance may make women BV-prone. A more recent characterization is that the human VMs can be classified into five major types, four of which possess type-specific dominant species of
Lactobacillus
. The remaining one (type IV) is not dominated by
Lactobacillus
and contains a handful of strictly anaerobic bacteria. Nevertheless, exceptions to the first hypothesis have been noticed from the very beginning, and there is not a definite relationship, suggested yet, between the five VM types and BV status. Here, we propose a novel hypothesis that assumes the existence of four VM types from dichotomous crisscrossing of “complex versus simple (high-diversity or low-dominance versus low-diversity or high-dominance)” on “healthy versus BV” (the four essential dimensions of VMs). We comprehensively test the hypothesis with 7,958 VM samples by demonstrating the statistically significant differences between the four VM types in community diversity, composition, dominance, heterogeneity, and stochasticity, and by identifying unique/enriched species in each VM type. We further verified the categorization (hypothesis) by using six machine learning (ML) algorithms, including deep learning artificial intelligence (AI) technology, to reclassify the randomly mixed VM samples into four respective types and achieved 85%–100% classification precisions. Our hypothesis provides a foundation for further investigating the etiology and automatic diagnosis of BV based on inexpensive amplicon sequencing and AI technology.

IMPORTANCE

BV may influence as many as one-third of women, but its etiology remains unclear. A traditional view is that dominance by
Lactobacillus
is the hallmark of a healthy vaginal microbiome and lack of dominance may make women BV-prone. Recent studies show that the human VMs can be classified into five major types, four of which possess type-specific dominant species of
Lactobacillus
. The remaining one (type IV) is not dominated by
Lactobacillus
and contains a handful of strictly anaerobic bacteria. Nevertheless, exceptions to the first hypothesis have been noticed from the very beginning, and there is not a definite relationship, suggested yet, between the five VM types and BV status. Here, we propose and test a novel hypothesis that assumes the existence of four VM types from dichotomous crisscrossing of “complex versus simple (high diversity or low dominance versus low diversity or high dominance)” on “healthy versus BV.” Consequently, there are simple BV versus complex BV.
Development of the early-life gut microbiome and associations with eczema in a prospective Chinese cohort
Authors: Cheung Man Kit , Leung Ting Fan , Tam Wing Hung , Leung Agnes S. Y. , Chan Oi Man , Ng Rita W. Y. , Yau Jennifer W. K. , Yuen Lai-yuk , Tong Sylvia L. Y. , Ho Wendy C. S. , Yeung Apple C. M. , Chen Zigui , Chan Paul K. S.
Published: August 2023

The first few years of life is a key period for the development of the gut microbiome. However, our current understanding of this topic is largely biased toward Western populations. In this study, we characterized the development and determinants of the gut microbiome in a prospective cohort of 112 term Chinese children by sequencing 713 stool samples collected at nine time points from birth to 3 years of age using 16S rRNA gene sequencing. We revealed alterations in the composition and alpha and beta diversities of the gut microbiota across the first 3 years of life. We identified mode of delivery, feeding mode, and intrapartum antibiotics as the major determinants of the early-life gut microbiome, the effects of all of which persisted up to 12 months. Importantly, by conducting a nested case–control study, we showed that alterations in the infant gut microbiota precede the development of eczema. Interestingly, we identified a depletion of
Bacteroides
and an enrichment of
Clostridium sensu stricto 1
in the gut microbiome of infants with eczema at 1 year old. The same patterns were also observed in C-section-born infants within the same time frames, suggesting a role of the gut microbiota in previously reported associations between C-section and increased risk of eczema. Our study has revealed important associations between the gut microbiome and eczema in infancy and has established the basis for potential prevention/treatment of eczema via modulation of the gut microbiota.

IMPORTANCE

Eczema is a major allergic disease in children, which is particularly prevalent in Chinese children during their first year of life. In this study, we showed that alterations in the infant gut microbiota precede the development of eczema in a prospective Chinese cohort. In particular, we discovered enrichments of the genera
Clostridium sensu stricto 1
and
Finegoldia
in the cases at 3 and 1 month of age, respectively, which may represent potential targets for intervention to prevent eczema. Besides, we identified a depletion of
Bacteroides
from 1 to 6 months of age and an enrichment of
Clostridium sensu stricto 1
at 3 months in the eczema cases, patterns also observed in C-section-born infants within the same time frames, providing first evidence to support a role of the gut microbiota in previously reported associations between C-section and increased risk of eczema in infancy.
Non-dermatologic isolated intracranial necrobiotic xanthogranuloma
Authors: Popoola Daniel , Housley Steven B , Jacoby Wady T , Lim Jaims , Cappuzzo Justin M , Levy Elad I
Published: August 2023

Necrobiotic xanthogranuloma is a condition that was first identified in 1980 based on its characteristic histological identity, and it has been known since then as a dermatologic manifestation of an underlying systemic dysproteinemia. Intracranial manifestation is a rare presentation of this condition and has been reported only once in its more than 40 years of existence. Herein and to our knowledge, we report the second observation of an intracranial manifestation and, surprisingly, the first case without the expected dermatologic and systemic dysproteinemia associations. This case identifies an existing knowledge gap in our understanding of necrobiotic xanthogranuloma and emphasises the need for further research into understanding the presentation, comorbidities and management of this condition.
Idiopathic hypereosinophilic syndrome presenting as cardiac tamponade and multiorgan dysfunction
Authors: Roth Kelly , Gupta Sushan , Paul Vishesh , Patel Priyank
Published: August 2023

Idiopathic hypereosinophilic syndrome is characterised by the overproduction of eosinophils with tissue infiltration, leading to multiorgan dysfunction. Its heterogenous presentation makes the diagnosis challenging and easy to miss. A woman in her 70s was admitted with chest pain and shortness of breath. Diagnostic testing showed elevated cardiac enzymes, an ejection fraction of 45% and pericardial effusion. Pericardiocentesis helped her symptoms significantly. Cardiac catheterisation revealed patent coronary arteries. She was diagnosed with myopericarditis and discharged on non-steroidal anti-inflammatory drugs. She returned the following week with worsening chest pain, dyspnoea and diarrhoea. Chest imaging showed bilateral infiltrates. Diagnostic testing showed eosinophilic predominance in peripheral blood (59%), pericardial fluid (37%) and bronchoalveolar lavage (31%). After a negative infectious workup, she was started on glucocorticoids and responded favourably. She was discharged on steroids. Mepolizumab was initiated outpatient, and steroids were discontinued. Mepolizumab was discontinued after 2 years while monitoring her symptoms and eosinophil counts.
Validation of a comorbidity questionnaire in patients with neurological disorders
Authors: Vijiaratnam Nirosen , Vadera Shree , Lefringhausen Katharina , Girges Christine , Schrag Anette
Published: August 2023

Rational

Several tools exist to assess comorbidities in neurological disorders, the most widely used being the Charlson Comorbidity Index (CCI), but it has several limitations. The Comorbidity and General Health Questionnaire (CGHQ) is a newly designed tool, which includes additional comorbidities associated with health-related quality of life (HR-QOL) and outcomes in neurological disorders.

Aims and objectives

To assess the feasibility and validity of the CGHQ in patients with neurological disease.

Method

Two hundred patients attending a general neurological clinic were invited to complete the CGHQ along with the EQ-5D-5L questionnaire. The CCI was simultaneously completed by the assessor. CGHQ comorbidity scores were compared with CCI, symptom burden and EQ-5D-5L scores.

Results

The CGHQ captured 22 additional comorbidities not included on the CCI and more comorbidities were endorsed on the CGHQ. The CGHQ correlated weakly to moderately with CCI comorbidity scores. While both the CGHQ and CCI correlated negatively with the EQ-5D-5L Visual Analogue Scale, only the CGHQ correlated negatively with the EQ-5D-5L summary index. The CGHQ but not the CCI correlated strongly and positively with symptom burden scores.

Conclusion

The CGHQ allows a more comprehensive assessment of comorbidities than the CCI and better correlates with patients’ overall symptom burden and HR-QOL in neurological patients.
Do markers of adiposity and glycaemia mediate the association between low carbohydrate diet and cardiovascular risk factors: findings from the UK National Diet and Nutrition Survey (NDNS) 2008–2016
Authors: Tramontt Cláudia Raulino , Mouti Saad , Lima Do Vale Marjorie , Li Xunhan , Golubic Rajna , Ray Sumantra
Published: August 2023

Objectives

To examine the associations between low carbohydrate diet (LCD) and conventional cardiovascular risk factors and investigate whether these associations are mediated by body mass index (BMI), waist circumference (WC) and haemoglobin A1c (HbA1c) applying causal mediation analyses.

Methods

We included 3640 adults aged 45–80 years from the UK National Diet and Nutrition Survey programme (2008–2016) with data on dietary intake, anthropometric and biochemical parameters. Four hypothetical interventions were examined: (1) LCD, (2) Low carbohydrate (LC) and high fibre diet (LCHF), (3) LC and high saturated fat diet (LCHS) and (4) LC and high unsaturated fat diet (LCHU). BMI and WC were used as markers of obesity. Biochemical markers included HbA1c, total cholesterol, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol, triglycerides, systolic and diastolic blood pressure and C reactive protein (CRP). BMI, WC and HbA1c were used as a mediator of the effects. The analysis was adjusted for sociodemographic characteristic, smoking, estimated total energy intake, alcohol consumption and antihypertensive medication. To identify a potential causal effect of LCD on cardiovascular disease (CVD) risk, we estimated the average treatment effect, and corresponding p values and CI for the total, indirect and direct effect of the treatment on the outcome.

Results

BMI, WC and HbA1c fully mediated the association between LCD and triglycerides and fully mediated the effects of LCHF on LDL, although BMI and WC were not sufficient to fully mediate the effects of LCHF on triglycerides and CRP. BMI alone fully mediated the effects of LCHS on HbA1c, triglycerides, LDL and CRP. None of these mediators explained the effect of LCHU on CVD risk markers.

Conclusion

The causal hypotheses tested in this study demonstrate that individuals on LCD with high fibre intakes improved their CVD markers as expected, but those on LCD who increase fat intake had no effects on CVD markers mediated by obesity and diabetes.
Resting-state electroencephalography theta predicts neurofeedback treatment 4-month follow-up response in nicotine addiction
Authors: Meng Qiujian , Zhu Ying , Yuan Ye , Yang Li , Liu Jiafang , Zhang Xiaochu , Bu Junjie
Published: August 2023

Background

The high rate of long-term relapse is a major cause of smoking cessation failure. Recently, neurofeedback training has been widely used in the treatment of nicotine addiction; however, approximately 30% of subjects fail to benefit from this intervention. Our previous randomised clinical trial (RCT) examined cognition-guided neurofeedback and demonstrated a significant decrease in daily cigarette consumption at the 4-month follow-up. However, significant individual differences were observed in the 4-month follow-up effects of decreased cigarette consumption. Therefore, it is critical to identify who will benefit from pre-neurofeedback.

Aims

We examined whether the resting-state electroencephalography (EEG) characteristics from pre-neurofeedback predicted the 4-month follow-up effects and explored the possible mechanisms.

Methods

This was a double-blind RCT. A total of 60 participants with nicotine dependence were randomly assigned to either the real-feedback or yoked-feedback group. They underwent 6 min closed-eye resting EEG recordings both before and after two neurofeedback sessions. A follow-up assessment was conducted after 4 months.

Results

The frontal resting-state theta power spectral density (PSD) was significantly altered in the real-feedback group after two neurofeedback visits. Higher theta PSD in the real-feedback group before neurofeedback was the only predictor of decreased cigarette consumption at the 4-month follow-up. Further reliability analysis revealed a significant positive correlation between theta PSD pre-neurofeedback and post-neurofeedback. A leave-one-out cross-validated linear regression of the theta PSD pre-neurofeedback demonstrated a significant correlation between the predicted and observed reductions in cigarette consumption at the 4-month follow-up. Finally, source analysis revealed that the brain mechanisms of the theta PSD predictor were located in the orbital frontal cortex.

Conclusions

Our study demonstrated changes in the resting-state theta PSD following neurofeedback training. Moreover, the resting-state theta PSD may serve as a prognostic marker of neurofeedback effects. A higher resting-state theta PSD predicts a better long-term response to neurofeedback treatment, which may facilitate the selection of individualised interventions.

Trial registration number

ChiCTR-IPR-17011710.
The times are changing: articulating the requisite leadership behaviours needed to embed equity, diversity and inclusivity into our healthcare systems
Authors: Straatman Lynn , Matlow Anne , Dickson Graham Stewart , Van Aerde John , Gautam Mamta
Published: August 2023

The last decade has opened many eyes and awakened many hearts to prevailing societal and global inequities. Major sociopolitical events of the past decade as well as the COVID-19 pandemic have highlighted demographic, racial, socioeconomical, geographical and other inequities with negative impact on health and wellbeing. Healthcare leaders, in the privileged position of influence, would benefit from an enhanced capabilities framework that articulates the specific actions and behaviours needed to embed equity, diversity and inclusivity (EDI) into their regular activities and ultimately into the healthcare system as a whole. The LEADS in a Caring Environment Capabilities Framework has been widely adopted in Canada and is similar to other national health leadership frameworks. Enhancements through an EDI lens are highly generalisable and can be contextually adapted to improve health, well-being and social justice worldwide.
Parity representation in leadership positions in academic medicine: a decade of persistent under-representation of women and Asian faculty
Authors: Samuel Anita , Soh Michael Y , Durning Steven J , Cervero Ronald M , Chen H Carrie
Published: August 2023

Purpose

In academic medicine, faculty from minority groups face discrepancy in career progression and few minorities rise to leadership positions in medical schools. The purpose of this exploratory study is to go beyond aggregate numbers and explore parity representation of different minority groups and women in leadership positions in medical schools. The primary research question of this study is: What is the level of parity representation in leadership positions at academic medical centres, examined by gender and by available race/ethnic categories?

Method

The Leadership Parity Index (LPI)—adapted from the Executive Parity Index—was used to calculate parity representation using national data obtained from the American Association of Medical College Faculty Roster for 2010–2021. Leadership was represented by department chairs and deans. Comparisons were made by gender and race/ethnicity.

Results

Within the datasets studied, the LPI for women and Asians was consistently below parity. Faculty who identified as White had LPIs above parity. When parsed by gender and race/ethnicity, Asian women had the lowest LPI of all race/ethnicities.

Discussion and conclusion

The ‘critical mass’ argument holds that when a group constitutes 30%–35% of the total, they would form a critical mass that would lead to more representation in leadership. Despite minority groups constituting said percentage, this study confirms that ‘critical mass’ has failed to lead to diversity in leadership. Furthermore, a focus on ‘critical mass’ obscures other disparities that exist within the system. The findings of this study show that aggregate data may not provide a true picture of equity and parity in medical schools. The variation in LPI within each race/ethnic group suggests that categories such as under-represented in medicine (URiM) and non-URiM, can mask differences within subgroups and should be applied with caution as they can have unintended consequences.
Estimated of CP violation in $$B^0$$ meson decays into $$D^{*+}$$ and $$D^-$$ mesons
Authors: Amirkhanlou Elnaz , Mohammadi Behnam
Published: August 2023

The decay $$B^0\rightarrow D^{*+}D^-$$

B
0

→

D

∗
+

D
-

is favorable mode for studying CP violation in the interference between mixing and decay for $$B^0$$

B
0

and $$\bar{B}^0$$

B

¯

0

mesons. The latest analysis of the CP parameters has been performed by the LHCb Collaboration values of $$S_{D^*D}=-\,0.861\pm 0.077\pm 0.019$$

S

D
∗

D

=
-

0.861
±
0.077
±
0.019

, $$C_{D^*D}=-\,0.059\pm 0.092\pm 0.020$$

C

D
∗

D

=
-

0.059
±
0.092
±
0.020

, $$\triangle S_{D^*D}=0.019\pm 0.075\pm 0.012$$

▵

S

D
∗

D

=
0.019
±
0.075
±
0.012

, $$\triangle C_{D^*D}=-\,0.031\pm 0.092\pm 0.016$$

▵

C

D
∗

D

=
-

0.031
±
0.092
±
0.016

, and $$\mathcal {A}_{D^*D}^{CP}=0.008\pm 0.014\pm 0.006\pm 0.003$$

A

D
∗

D

CP

=
0.008
±
0.014
±
0.006
±
0.003

. We have been estimated the parameters $$S_{D^*D}$$

S

D
∗

D

and $$C_{D^*D}$$

C

D
∗

D

of the $$B^0\rightarrow D^{*+}D^-$$

B
0

→

D

∗
+

D
-

decay as $$-\,0.709\pm 0.024$$

-

0.709
±
0.024

and $$-\,0.051\pm 0.004$$

-

0.051
±
0.004

. In the following, we have obtained the values of $$\triangle S_{D^*D}=0.054\pm 0.003$$

▵

S

D
∗

D

=
0.054
±
0.003

and $$\triangle C_{D^*D}=0.020\pm 0.001$$

▵

C

D
∗

D

=
0.020
±
0.001

and direct CP violation of $$0.008\pm 0.001$$

0.008
±
0.001

. Also, we have calculated the branching ratio of $$B^0\rightarrow D^{*+}D^-$$

B
0

→

D

∗
+

D
-

decay. The values obtained in this work are comparable with the corresponding experimental values.
Electron capture and ionisation in He$$^{2+}$$ collisions with H$$_2$$
Authors: Kotian Aks M. , Plowman Corey T. , Kadyrov Alisher S.
Published: August 2023

State-selective non-dissociative electron capture and ionisation cross sections are calculated for collisions between bare helium-ions and molecular hydrogen. The two-centre wave-packet convergent close-coupling approach is used and the hydrogen molecule is represented as an effective one-electron target. For the electron-capture cross section, our results are in good agreement with experimental measurements at energies above 100 keV/u. However, near the peak of the cross section, they are larger than the experimental data. The total ionisation cross section is also in good agreement with experiment, particularly at low and high energies. The results for the state-selective electron-capture cross section are generally in good agreement with the limited experimental measurements. However, we find that our results appear to consistently overestimate the experimental data for electron capture into the s states at intermediate energies. The present results are the first calculations capable of producing electron capture and ionisation cross sections over a wide incident energy range within a single unified theoretical framework.

Graphical Abstract
A Recursive Algorithm for Constructing Dual-CISTs in Hierarchical Folded Cubic Networks
Authors: Lin Hsin-Jung , Tang Shyue-Ming , Pai Kung-Jui , Chang Jou-Ming
Published: August 2023

Let [Formula: see text] be a set of [Formula: see text] spanning trees in a graph [Formula: see text]. The [Formula: see text] spanning trees are called completely independent spanning trees (CISTs for short) if the paths joining every pair of vertices [Formula: see text] and [Formula: see text] in any two trees have neither vertex nor edge in common except for [Formula: see text] and [Formula: see text]. Particularly, [Formula: see text] is called a dual-CIST provided [Formula: see text]. For data transmission applications in reliable networks, the existence of a dual-CIST can provide a configuration of fault-tolerant routing called protection routing. This paper investigates the problem of constructing a dual-CIST in the [Formula: see text]-dimensional hierarchical folded cubic network [Formula: see text]. The network is a two-level network using folded hypercube [Formula: see text] as clusters to reduce the diameter, hardware overhead and improve the fault tolerance ability. We propose a recursive algorithm to construct a dual-CIST of [Formula: see text] in [Formula: see text] time for [Formula: see text], where the time required is the same scale as the number of vertices of [Formula: see text]. Also, the diameter of each constructed CIST is [Formula: see text].
Pharmacological Benefits and Underlying Mechanisms of Salvia miltiorrhiza against Molecular Pathology of Various Liver Diseases: A Review
Authors: Hwang Cho Hyun , Jang Eungyeong , Lee Jang-Hoon
Published: August 2023

Salvia miltiorrhiza Bunge, called Danshen in Chinese, is the dried root and rhizome of S. miltiorrhiza, which is part of the mint family, Lamiaceae; it has chiefly been used to treat blood stasis and improve blood flow in cerebrovascular and cardiovascular diseases for over 2000 years. Recent preclinical studies have indicated that S. miltiorrhiza has a wide range of pharmacological properties making it useful for the treatment of diverse liver diseases. S. miltiorrhiza protects the liver from harmful hepatotoxins, reduces hepatic oxidative stress, ameliorates steatosis, and alleviates hepatic inflammation, fibrosis, and cancer. Moreover, several key mechanisms, including apoptosis, AMP-activated protein kinase, mitogen-activated protein kinase, and nuclear factor kappa B, may be involved in the benefits of S. miltiorrhiza in hepatic disorders. In particular, salvianolic acid B and cryptotanshinone, both compounds derived from S. miltiorrhiza, possess therapeutic activities similar to those of S. miltiorrhiza, and thus may play a crucial role in the therapeutic activity of S. miltiorrhiza in liver diseases. Because reports on the pharmacological effects of this herb are scattered, this review aimed to consolidate the available literature to allow the re-evaluation and identification of gaps to guide future research. This review focuses on the role of S. miltiorrhiza in improving the molecular pathology of liver diseases, as reported in in vitro and in vivo studies.
Bergenin Inhibits Tumor Growth and Overcomes Radioresistance by Targeting Aerobic Glycolysis
Authors: Li Xiaoying , Xie Li , Zhou Li , Gan Yu , Han Shuangze , Zhou Yuanfeng , Qing Xiang , Li Wei
Published: August 2023

Hexokinase 2 (HK2), the first glycolytic rate-limiting enzyme, is closely correlated with the occurrence and progression of tumors. Effective therapeutic agents targeting HK2 are urgently needed. Bergenin has exhibited various pharmacological activities, such as antitumor properties. However, the effects of bergenin on the abnormal glucose metabolism of cancer cells are yet unclear. In this study, HK2 was overexpressed in OSCC tissues, and the depletion of HK2 inhibited the growth of OSCC cells in vitro and in vivo. Moreover, these results showed that the natural compound, bergenin, exerted a robust antitumor effect on OSCC cells. Bergenin inhibited cancer cell proliferation, suppressed glycolysis, and induced intrinsic apoptosis in OSCC cells by downregulating HK2. Notably, bergenin restored the antitumor efficacy of irradiation in the radioresistant OSCC cells. A mechanistic study revealed that bergenin upregulated the protein level of phosphatase and the tensin homolog deleted on chromosome 10 (PTEN) by enhancing the interaction between PTEN and ubiquitin-specific protease 13 (USP13) and stabilizing PTEN; this eventually inhibited AKT phosphorylation and HK2 expression. Bergenin was identified as a novel therapeutic agent against glycolysis to inhibit OSCC and overcome radioresistance. Targeting PTEN/AKT/HK2 signaling could be a promising option for clinical OSCC treatment.
A Survey of Controllable Text Generation Using Transformer-based Pre-trained Language Models
Authors: Zhang Hanqing , Song Haolin , Li Shaoyu , Zhou Ming , Song Dawei
Published: August 2023

Controllable Text Generation (CTG) is an emerging area in the field of natural language generation (NLG). It is regarded as crucial for the development of advanced text generation technologies that better meet the specific constraints in practical applications. In recent years, methods using large-scale pre-trained language models (PLMs), in particular the widely used Transformer-based PLMs, have become a new paradigm of NLG, allowing generation of more diverse and fluent text. However, due to the limited level of interpretability of deep neural networks, the controllability of these methods needs to be guaranteed. To this end, controllable text generation using Transformer-based PLMs has become a rapidly growing yet challenging new research hotspot. A diverse range of approaches have emerged in the past 3 to 4 years, targeting different CTG tasks that require different types of controlled constraints. In this article, we present a systematic critical review on the common tasks, main approaches, and evaluation methods in this area. Finally, we discuss the challenges that the field is facing, and put forward various promising future directions. To the best of our knowledge, this is the first survey article to summarize the state-of-the-art CTG techniques from the perspective of Transformer-based PLMs. We hope it can help researchers and practitioners in the related fields to quickly track the academic and technological frontier, providing them with a landscape of the area and a roadmap for future research.
Survey on Secure Keyword Search over Outsourced Data: From Cloud to Blockchain-assisted Architecture
Authors: Wu Haiqin , Düdder Boris , Wang Liangmin , Cao Zhenfu , Zhou Jun , Feng Xia
Published: August 2023

Secure keyword search is a prevailing search service offered in outsourced environments. However, with the increasingly severe security vulnerabilities of conventional centralized outsourcing, the architecture of secure keyword search, with searchable encryption (SE) as the underlying technique, has recently shifted from cloud-centered models to blockchain-assisted models. Existing surveys commonly fail to capture such an evolution and the corresponding benefits. What on earth does blockchain bring about and what are the unexplored challenges? This survey provides a systematic review of secure keyword search over outsourced data from cloud to blockchain-assisted architectures. We propose a taxonomy assorting present studies, depending on whether cloud/blockchain and data sharing are included, in which blockchain-assisted architecture is further divided into blockchain-side and cloud-side keyword search, respectively. Technically, we conclude five types of representative SE techniques with fitting architectures, either cryptographic-based or hardware-dependent. Notably, we propose comprehensive methodologies to select relevant papers, discuss, and compare existing schemes regarding functionalities, security, efficiency, and fairness (up to 21 compared items). Finally, open issues and potential research directions are identified for future work. We aspire to help pave the way for addressing the theoretical and empirical aspects of secure keyword search and full-fledged real-world implementation of blockchain-based keyword search applications.
Mitigation of Concurrent Flood and Drought Risks Through Land Modifications: Potential and Perspectives of Land Users
Authors: Slavíková Lenka , Milman Anita
Published: August 2023

Modifications to land can serve to jointly reduce risks of floods and droughts to people and to ecosystems. Whether land modifications are implemented will depend on the willingness and ability of a diversity of actors. This article reviews the state of knowledge on land modification use in areas exposed to dual hydrologic risks and the land owners, managers, and users who directly make decisions about action on lands they control. The review presents a typology of land modifications and explains how land modifications interact with the hydrological cycle to reduce risks. It then addresses the roles and perspectives of the land owners, managers, and users undertaking land modifications, summarizing theories explaining motivations for, as well as barriers to and enablers of, land modification implementation. The analysis reveals geographical differences in narratives on land modifications as well as knowledge gaps regarding variation across actors and types of land modifications.
A Solvent-Free Process Enabled by Polytetrafluoroethlyene/Carbon Black Composites for Fabricating Electrodes for Lithium-Ion Batteries with a High Volumetric Energy
Authors: Choi Hyeongjun , Moon Dongjun , Sheem Junmyoung , Koo Jin Kyo , Hong Seungmin , Oh Seung-Min , Kim Young-Jun
Published: August 2023

Manufacturing electrodes for lithium-ion batteries (LIBs) consists of making a slurry, coating the slurry onto a current collector, drying the slurry to remove the solvent, and calendaring the electrode. Cathodes for LIBs are fabricated by a wet process using a toxic chemical, N-methyl-2-pyrrolidone (NMP). However, it is preferable to use a dry process without toxic chemicals, and with fewer manufacturing operations, which saves money. However, the powder-mixing step of the dry process makes it difficult to ensure a uniform distribution of the carbonaceous conducting agents and binder used, which agglomerate in the dry mixed product. To solve this problem, we fabricate a composite of polytetrafluoroethylene (PTFE) and carbon black (CB) nanoparticles. The electrode fabricated using the PTFE/CB composite has a 98 wt% active material content and 3.8 g cc−1 of electrode density. An electrode produced by the conventional wet process using a polyvinylidene fluoride (PVDF) binder and NMP solvent has a 96 wt% active material content and an electrode density of 3.4 g cc−1. The dry-processed electrode has a higher volumetric capacity (760 mAh cc−1) as well as a higher discharge rate capability and cycle life than a conventional wet-processed electrode.
A Comprehensive Computational Fluid Dynamics Modeling of Lithium Sulphate Electrodialysis
Authors: Asadi Anahita , Harandi Hesam Bazargan , Kang Bolin , Jung Joey Chung-Yen , Sui Pang-Chieh
Published: August 2023

As a part of the recycling process of spent lithium-ion batteries, electrodialysis (ED) is used to extract lithium hydroxide and sulfuric acid from the lithium sulphate solution. This study reports on a multicomponent, 2-dimensional ED model based on simultaneously solving the Nernst-Planck equation, Navier–Stokes equations, species conservation with electrochemical reactions, and electro-osmotic water flow equations using computational fluid dynamics technique. To satisfy the electroneutrality assumption in the ED device, the fluxes of H+ and OH− ions produced from electrochemical reactions are estimated. The distributions of velocity, potential, and species’ concentrations are determined. A close agreement between the present model and experimental data shows the accuracy and validity of this work. The influence of transmembrane water flow is investigated. It is revealed that although the water molecules transferring from dilute to concentrate compartments reduce the concentration of concentrate channels, the generated ionic convection flux reversely affects this quantity. A parametric study is carried out to study the effects of operation conditions and membrane properties. It is found that 37% growth of dilute channel concentration is observed when inlet velocity increases from 50 to 100 μm·s−1. The enhancement of the water volume fraction of membranes also reduces the transmembrane water flow rate.