bluuebunny/crossref_metadata_2025 huggingface dataset:
Is orthodontic research falling prey to obscure and predatory journals? A bibliometric study
Authors: Maroulakos Michael P , Al-Moghrabi Dalya , Fleischmann Isabel , Pandis Nikolaos , Fleming Padhraig S
Published: September 2024

Aims

To evaluate where orthodontic research papers are published and to explore potential relationships between the journal of publication and the characteristics of the research study and authorship.

Methods

An online literature search of seven research databases was undertaken to identify orthodontic articles published in English language over a 12-month period (1 January–31 December 2022) (last search: 12 June 2023). Data extracted included journal, article, and author characteristics. Journal legitimacy was assessed using a ternary classification scheme including available blacklists and whitelists, cross-checking of indexing claims and history of sending unsolicited emails. The level of evidence (LOE) of all included studies was assessed using a modified Oxford LOE classification scale. Univariable and multivariable ordinal logistic regression analyses were performed to examine possible associations between the level of evidence, journal discipline, and authorship characteristics.

Results

A total of 753 studies, published by 246 unique journal titles, were included and further assessed. Nearly two-thirds of orthodontic papers were published in non-orthodontic journals (62.8%) and over half (55.6%) of the articles were published in open-access policy journals. About a fifth of the articles (21.2%) were published either in presumed predatory journals or in journals of uncertain legitimacy. Journal discipline was significantly associated with the level of evidence. Higher-quality orthodontic studies were more likely published in established orthodontic journals (likelihood ratio test P < .001).

Limitations

The identification and classification of predatory journals are challenging due to their covert nature.

Conclusions

The majority of orthodontic articles were published in non-orthodontic journals. In addition, approximately one in five orthodontic studies were published in presumed predatory journals or in journals of uncertain legitimacy. Studies with higher levels of evidence were more likely to be published in established orthodontic journals.
Apple vacuolar sugar transporters regulated by MdDREB2A enhance drought resistance by promoting accumulation of soluble sugars and activating ABA signaling
Authors: Zhu Lingcheng , Zhang Chunxia , Yang Nanxiang , Cao Wenjing , Li Yanzhen , Peng Yunjing , Wei Xiaoyu , Ma Baiquan , Ma Fengwang , Ruan Yong-Ling , Li Mingjun
Published: September 2024

Soluble sugars are not only an important contributor to fruit quality, but also serve as the osmotic regulators in response to abiotic stresses. Early drought stress promotes sugar accumulation, while specific sugar transporters govern the cellular distribution of the sugars. Here, we show that apple plantlets accumulate soluble sugars in leaf tissues under drought stress. Transcriptional profiling of stressed and control plantlets revealed differential expression of several plasma membrane—or vacuolar membrane-localized sugar transporter genes. Among these, four previously identified vacuolar sugar transporter (VST) genes (MdERDL6–1, MdERDL6–2, MdTST1, and MdTST2) showed higher expression under drought, suggesting their roles in response to drought stress. Promoter cis-elements analyses, yeast one-hybrid, and dual-luciferase tests confirmed that the drought-induced transcription factor MdDREB2A could promote the expression of MdERDL6–1/−2 and MdTST1/2 by binding to their promoter regions. Moreover, overexpressing of each of these four MdVSTs alone in transgenic apple or Arabidopsis plants accumulated more soluble sugars and abscisic acid (ABA), and enhanced drought resistance. Furthermore, apple plants overexpressing MdERDL6–1 also showed reduced water potential, facilitated stomatal closure, and reactive oxygen species scavenging under drought conditions compared to control plants. Overall, our results suggest a potential strategy to enhance drought resistance and sugar accumulation in fruits through manipulating the genes involved in vacuolar sugar transport.
Redefining cross-resistance, co-resistance and co-selection: beyond confusion?
Authors: Simjee Shabbir , Weese J Scott , Singh Ruby , Trott Darren J , Essack Sabiha , Chuanchuen Rungtip , Mehrotra Shubhi
Published: September 2024

The similarity of current definitions of ‘cross-resistance’ and ‘co-resistance’ continues to cause confusion both in the scientific community as well as in understanding policies and in particular when looking at resistance from a risk assessment perspective. Further, lack of harmonized definitions of these terms in the regulatory space is challenging for interpretation. The purpose of this article is to: (i) provide an overview of the ambiguity in existing terminology related to cross-resistance, co-resistance and co-selection; (ii) emphasize the challenges created by the use of poor terminology in research and scientific literature; and (iii) propose a clear set of harmonized definitions that could be put into use through international regulatory agencies and institutions, such as the World Health Organization, Food and Drug Administration, European Medicines Agency, Center for Disease Control, Committee for Veterinary Medicinal Products, World Organization for Animal Health/Office International des Epizooties and the Food and Agriculture Organization of the United Nations.
Potential prognostic predictors of treatment with immune checkpoint inhibitors for advanced endometrial cancer
Authors: Yanazume Shintaro , Nagata Chikako , Kobayashi Yusuke , Fukuda Mika , Mizuno Mika , Togami Shinichi , Kobayashi Hiroaki
Published: September 2024

Background

Prognostic predictors of immunotherapy in patients with advanced endometrial cancer remain unclear. The potential role of inflammatory predictors, including pretreatment neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and hemoglobin, albumin, lymphocyte and platelet scores, was investigated.

Methods

Between August 2018 and December 2023, 35 patients were retrospectively analyzed. Prognostic predictors were compared, and optimal cut-off values that exhibited the greatest discrimination for overall response, disease control, progression-free survival and overall survival were determined. Multivariate analysis was used to assess the prognostic significance of the predictors.

Results

The greatest discrimination for overall response, progression-free survival and overall survival included platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio and hemoglobin, albumin, lymphocyte and platelet; the areas under the curve were 0.638, 0.649 and 0.641, respectively. The precise cut-off values of neutrophil-to-lymphocyte ratio for progression-free survival and overall survival were 4.92 and 5.40, respectively. The lower neutrophil-to-lymphocyte ratio group had a significantly longer progression-free survival (P = 0.001, median survival; 4.0 months vs. 19 months) and longer overall survival (P = 0.002, median survival; 5.0 months vs. 21 months). Of the risk factors assessed, neutrophil-to-lymphocyte ratio (hazard ratio = 4.409; 95% CI = 1.10–17.64; P = 0.036) and regimen (hazard ratio = 5.559; 95% CI = 1.26–24.49; P = 0.023) were independently correlated with overall survival.

Conclusion

In patients with advanced endometrial cancer, pretreatment neutrophil-to-lymphocyte ratio may be a prognostic predictor of those who would benefit from immunotherapy.
Kidney Sales and Disrespectful Demands: A Reply to Rippon
Authors: Semrau Luke
Published: September 2024

Simon Rippon, revising an earlier argument against kidney sales, now claims that offers involving the performance of invasive acts, when extended to people under pressure, constitute a kind of rights violation, Impermissibly Disrespectful Demands. Since offers involving kidney sales so qualify, Rippon finds prima facie reason to prohibit them. The present article levels four independent objections to Rippon’s argument: the account of Impermissibly Disrespectful Demands implausibly condemns kidney donation as much as kidney sales; the normative importance of having autonomous veto control over bodily incursions does not plausibly underwrite a right to not be extended invasive offers under pressure; Impermissibly Disrespectful Demands can easily be transformed into innocuous offers; and the prohibition has greater welfare costs than Rippon acknowledges.
Accelerating progress to reduce the cancer burden through prevention and control in the United States
Authors: Goddard Katrina A B , Feuer Eric J , Umar Asad , Castle Philip E
Published: September 2024

Improvements in cancer prevention and control are poised to be main contributors in reducing the burden of cancer in the United States. We quantify top opportunities to accelerate progress using projected life-years gained and deaths averted as measures. We project that over the next 25 years, realistic gains from tobacco control can contribute 0.4-17 million additional life-years gained per intervention and 8.4 million additional life-years gained from improving uptake of screening programs over the lifetime of 25 annual cohorts. Additional opportunities include addressing modifiable risk factors (excess weight, alcohol consumption), improving methods to prevent or treat oncogenic infections, and reducing cancer health disparities. Investment is needed in the pipeline of new preventive agents and technologies for early detection to continue progress. There is also a need for additional research to improve the access to and uptake of existing and emerging interventions for cancer prevention and control and to address health disparities. These gains are undeniably within our power to realize for the US population.
Hypoactive sexual desire disorder in women: new possibilities to ensure better understanding, diagnosis, and response to treatment
Authors: Maseroli Elisa , Cipriani Sarah , Lanzi Valeria , Ravelli Serena Anna , Annunziato Mattia , Alfaroli Chiara , Lippi Donatella , Cirillo Michela , Castellini Giovanni , Giraldi Annamaria , Maggi Mario , Vignozzi Linda
Published: September 2024

Background

Hypoactive Sexual Desire Disorder (HSDD) is a frequent sex-related problem in women; however, a specific tool to characterize HSDD subtypes based on sexual inhibitory and excitatory factors is still lacking.

Aim

(1) To find a cutoff value in Sexual Inhibition Scale (SIS)/Sexual Excitation Scale (SES) scores predicting a diagnosis of HSDD in women consulting for sexual symptoms, (2) to explore the sexual inhibitory and excitatory profiles in women referred to a clinic for female sexual dysfunction by stratifying the sample according to the newfound cutoffs, and (3) to identify biopsychosocial factors significantly associated with the 2 profiles.

Methods

An overall 133 women consulting for sexual symptoms were retrospectively evaluated for clinical, biochemical, and psychosexologic data collected at the first visit. A subgroup of 55 women treated with transdermal testosterone was retrospectively analyzed at baseline and the 6-month visit.

Outcomes

Patients underwent physical and laboratory examinations and completed the SIS/SES, Female Sexual Function Index, Female Sexual Distress Scale–Revised, Emotional Eating Scale, and Middlesex Hospital Questionnaire.

Results

Specific cutoffs for SIS1 (≥32.5; indicating threat of performance failure) and SES (≤46.5) predicted HSDD diagnosis with an accuracy of 66.4% (P = .002) and 68.7% (P < .0001), respectively. Patients with impaired SIS1 scores showed higher distress and psychopathologic symptoms, while those with impaired SES scores demonstrated lower desire and arousal and a negative association with some metabolic and hormonal parameters. SES score also showed a significant predictive value on testosterone treatment efficacy for HSDD.

Clinical Translation

A better characterization of HSDD would enable individualized treatment based on the main underlying etiologies.

Strengths and Limitations

Limitations of the study include the small sample size and cross-sectional retrospective design, with the choice of treatment for HSDD limited to transdermal testosterone. Strengths comprise the thorough and multifactorial evaluation of every aspect potentially affecting inhibitory and excitatory components of sexual desire.

Conclusion

Validated cutoffs of SIS/SES scores could allow deep characterization of women diagnosed with HSDD, thus ensuring better tailoring of therapy and prediction of the probability of response to specific treatments.
Incidence of and predictive factors for lung cancer in patients with rheumatoid arthritis: A retrospective long-term follow-up study
Authors: Mori Shunsuke , Hasegawa Mizue , Sakai Fumikazu , Nakashima Kouya , Nakamura Kazuyoshi
Published: September 2024

Objectives

The aim of this study was to determine the incidence and predictive factors of lung cancer in rheumatoid arthritis (RA).

Methods

We conducted a retrospective follow-up study of patients who were diagnosed with RA at our institution between April 2001 and December 2022. Pulmonary complications were evaluated using high-resolution computed tomography (HRCT) at RA diagnosis. Patients were followed until the diagnosis of lung cancer, diagnosis of other malignancies, death, loss to follow-up, or the end of the study.

Results

Among 771 RA patients, 3.5% were diagnosed with combined pulmonary fibrosis and emphysema (CPFE), 4.9% with interstitial lung disease (ILD) alone, and 6.0% with emphysema alone. During follow-up (mean of 9.3 years), the crude incidence rates of lung cancer per 1000 patient-years were 2.9 in all patients, 47.8 in CPFE patients, 10.5 in ILD patients, 11.9 in emphysema patients, and 0.8 in patients without these complications. Only male patients showed a higher incidence of lung cancer compared with the general population. In multivariable Fine–Gray regression analysis, the presence of HRCT-proven CPFE, ILD, and emphysema, and smoking history were identified as predictive factors for lung cancer in RA patients.

Conclusions

Close monitoring of lung cancer is needed for RA patients with smoking history and pulmonary complications, especially CPFE.
Structural basis of DNA recognition by BEN domain proteins reveals a role for oligomerization in unmethylated DNA selection by BANP
Authors: Ren Jiahao , Wang Junmeng , Ren Yanpeng , Zhang Yuyang , Wei Pengshuai , Wang Meng , Zhang Yimeng , Li Meng , Yuan Chuyan , Gong Haipeng , Jiang Junyi , Wang Zhanxin
Published: September 2024

The BEN domain is a newly discovered type of DNA-binding domain that exists in a variety of species. There are nine BEN domain-containing proteins in humans, and most have been shown to have chromatin-related functions. NACC1 preferentially binds to CATG motif-containing sequences and functions primarily as a transcriptional coregulator. BANP and BEND3 preferentially bind DNA bearing unmethylated CpG motifs, and they function as CpG island-binding proteins. To date, the DNA recognition mechanism of quite a few of these proteins remains to be determined. In this study, we solved the crystal structures of the BEN domains of NACC1 and BANP in complex with their cognate DNA substrates. We revealed the details of DNA binding by these BEN domain proteins and unexpectedly revealed that oligomerization is required for BANP to select unmethylated CGCG motif-containing DNA substrates. Our study clarifies the controversies surrounding DNA recognition by BANP and demonstrates a new mechanism by which BANP selects unmethylated CpG motifs and functions as a CpG island-binding protein. This understanding will facilitate further exploration of the physiological functions of the BEN domain proteins in the future.
Tuberculosis and Chronic Hepatitis B Virus Infection Screening Among Non-US–Born Persons in an Integrated Health System in California
Authors: Wick Jenna M , Ni Yuching , Halmer Nicole , Wong Robert J , Chitnis Amit S , Jaganath Devan , Krueger Amy L , Skarbinski Jacek
Published: September 2024

Background

Tuberculosis infection (TBI) and chronic hepatitis B virus (HBV) infection disproportionately affect non–US-born persons. Early identification and treatment are critical to reduce transmission, morbidity, and mortality, but little is known about screening in the United States.

Methods

We conducted a cross-sectional study in a large integrated California health system in September 2022 assessing TBI and HBV screening among persons aged ≥18 years who were born in countries with high TB burden (TB disease incidence rates ≥20/100 000 population) and/or HBV burden (hepatitis B surface antigen seroprevalence >2%).

Results

Of 510 361 non–US-born persons born in countries with high TB burden, 322 027 (63.1%) were born in countries with high HBV burden and 188 334 (36.9%) in countries with only high TB burden. Among persons born in countries with high TB and HBV burden, 29.6% were screened for TBI, 64.5% for HBV, and 23.4% for TBI and HBV; 9.9% had TBI and 3.1% had HBV infection. Among persons born in countries with high TB burden only, 27.9% were screened for TBI and 7.5% had TBI.

Conclusions

Among non–US-born persons from countries with high TB and HBV burden, we found low screening rates and elevated prevalence of TBI and chronic HBV infection. Cotesting for TBI and HBV infection in non–US-born persons from countries with high TB and HBV burden might improve outcomes by identifying persons who warrant TBI treatment, HBV treatment, or HBV vaccination. Increased screening is the first step in reducing health inequities and overall disease burden.
Age-related differences in the prevalence of premature ejaculation: taking a second and more detailed look
Authors: Rowland David L , Kӧvi Zsuzsanna , Hevesi Krisztina
Published: September 2024

Background

Research indicates an inconsistent relationship between age and the prevalence of premature ejaculation (PE), with studies reporting an increase, decrease, or no change with age.

Aim

To reexamine the possible relationship between age and PE prevalence, implementing methodological improvements that enhance the likelihood of detecting real effects.

Methods

From a sample of 2772 men, we analyzed a subset of 418 classified as having probable or definite PE based on the Premature Ejaculation Diagnostic Tool. We not only analyzed men with lifelong PE (LPE; n = 316) and acquired PE (APE; n = 102) separately but assessed prevalence differences across age groups using an omnibus measure to establish PE status and specific PE diagnostic criteria, individually and in multifactorial combination.

Outcome

Prevalence of PE in younger vs older men.

Results

LPE, but not APE, showed age-related differences in prevalence, with LPE being lower in the higher age group. This pattern was most discernible when a multifactorial approach was used to establish PE status.

Clinical Translation

Older men may be less distressed about their dysfunction or may benefit from diminishing ejaculatory function with age.

Strengths and Limitations

This cross-sectional study used an improved methodology to detect age-related differences in PE prevalence. Future studies would benefit from a larger sample size that enables a breakdown of prevalence using a greater number of age categories.

Conclusion

According to an improved methodology, men with LPE showed a decline in prevalence with aging. A methodology aimed at exploring this relationship should—at the very least—not only distinguish between LPE and APE subtypes but also consider using a multifactorial method of determining PE status that includes a measure of bother/distress.
SHP2 ablation mitigates osteoarthritic cartilage degeneration by promoting chondrocyte anabolism through SOX9
Authors: Wang Lijun , Yang Huiliang , Wang Changwei , Wang Mingliang , Huang Jiahui , Nyunt Thedoe , Osorio Camilo , Sun Shi‐Yong , Pacifici Maurizio , Lefebvre Véronique , Moore Douglas C. , Wang Shaomeng , Yang Wentian
Published: September 2024

Articular cartilage phenotypic homeostasis is crucial for life‐long joint function, but the underlying cellular and molecular mechanisms governing chondrocyte stability remain poorly understood. Here, we show that the protein tyrosine phosphatase SHP2 is differentially expressed in articular cartilage (AC) and growth plate cartilage (GPC) and that it negatively regulates cell proliferation and cartilage phenotypic program. Postnatal SHP2 deletion in Prg4+ AC chondrocytes increased articular cellularity and thickness, whereas SHP2 deletion in Acan+ pan‐chondrocytes caused excessive GPC chondrocyte proliferation and led to joint malformation post‐puberty. These observations were verified in mice and in cultured chondrocytes following treatment with the SHP2 PROTAC inhibitor SHP2D26. Further mechanistic studies indicated that SHP2 negatively regulates SOX9 stability and transcriptional activity by influencing SOX9 phosphorylation and promoting its proteasome degradation. In contrast to published work, SHP2 ablation in chondrocytes did not impact IL‐1‐evoked inflammation responses, and SHP2's negative regulation of SOX9 could be curtailed by genetic or chemical SHP2 inhibition, suggesting that manipulating SHP2 signaling has translational potential for diseases of cartilage dyshomeostasis.
SCG2 mediates blood–brain barrier dysfunction and schizophrenia‐like behaviors after traumatic brain injury
Authors: Lin Chao , Zhao Pengzhang , Sun Guangchi , Liu Ning , Ji Jing
Published: September 2024

Traumatic brain injury (TBI), which is characterized by acute neurological dysfunction, is also one of the most widely recognized environmental risk factors for various neurological and psychiatric disorders. However, the role of TBI in neurological perturbation and the mechanisms underlying these disorders remain unknown. We evaluated transcriptional changes in cells of the frontal cortex after TBI by exploiting single‐cell RNA sequencing (scRNA‐Seq). We adopted the gene expression omnibus and scRNA‐Seq to identify the mediation by secretogranin II (SCG2) of TBI‐induced schizophrenia. Astrocytes are a principal source of SCG2 in the frontal cortex after TBI. Our analysis indicated that SCG2‐triggered disruption of the blood–brain barrier (BBB) via the CypA‐MMP‐9 signaling pathway. Furthermore, astrocytic SCG2 knockout in the frontal cortex reduced BBB damage, mitigated inflammation, and inhibited schizophrenia after TBI. In conclusion, we identified the SCG2‐CypA‐MMP‐9 signaling pathway in reactive astrocytes as a key switch in the protection of the BBB and provided a novel therapeutic avenue for treating psychiatric disorders after TBI.
Evaluation of the prostate cancer and its metastases in the [68Ga]Ga-PSMA PET/CT images: deep learning method vs. conventional PET/CT processing
Authors: Dorri Giv Masoumeh , Arabi Hossein , Naseri Shahrokh , Alipour Firouzabad Leila , Aghaei Atena , Askari Emran , Raeisi Nasrin , Saber Tanha Amin , Bakhshi Golestani Zahra , Dabbagh Kakhki Amir Hossein , Dabbagh Kakhki Vahid Reza
Published: September 2024

Purpose

This study demonstrates the feasibility and benefits of using a deep learning-based approach for attenuation correction in [68Ga]Ga-PSMA PET scans.

Methods

A dataset of 700 prostate cancer patients (mean age: 67.6 ± 5.9 years, range: 45–85 years) who underwent [68Ga]Ga-PSMA PET/computed tomography was collected. A deep learning model was trained to perform attenuation correction on these images. Quantitative accuracy was assessed using clinical data from 92 patients, comparing the deep learning-based attenuation correction (DLAC) to computed tomography-based PET attenuation correction (PET-CTAC) using mean error, mean absolute error, and root mean square error based on standard uptake value. Clinical evaluation was conducted by three specialists who performed a blinded assessment of lesion detectability and overall image quality in a subset of 50 subjects, comparing DLAC and PET-CTAC images.

Results

The DLAC model yielded mean error, mean absolute error, and root mean square error values of −0.007 ± 0.032, 0.08 ± 0.033, and 0.252 ± 125 standard uptake value, respectively. Regarding lesion detection and image quality, DLAC showed superior performance in 16 of the 50 cases, while in 56% of the cases, the images generated by DLAC and PET-CTAC were found to have closely comparable quality and lesion detectability.

Conclusion

This study highlights significant improvements in image quality and lesion detection capabilities through the integration of DLAC in [68Ga]Ga-PSMA PET imaging. This innovative approach not only addresses challenges such as bladder radioactivity but also represents a promising method to minimize patient radiation exposure by integrating low-dose computed tomography and DLAC, ultimately improving diagnostic accuracy and patient outcomes.
The evolving world of the urinary microbiome
Authors: Dalvi Hrishikesh , De Nisco Nicole J.
Published: September 2024

Purpose of review

The existence of urinary microbiome in healthy individuals is now widely accepted as the longstanding belief in urinary tract sterility was disproved over a decade ago. The urinary microbiome has since been implicated in multiple urologic conditions including urinary tract infection (UTI), urinary incontinence, and bladder cancer. This review relays new findings of urinary microbiome compositional changes associated with aging and UTI susceptibility.

Recent findings

Recent advancements have established how the urinary microbiome changes over the lifespan. Studies finding distinct urinary microbiomes in prepubescent, reproductive age, and postmenopausal females have identified sex hormones as potential modulators of urinary microbiome composition and have identified prevalent species that may be markers of dysbiosis. Research in male children finds a cultivable urinary microbiota that varies with age or urologic history but not delivery mode. Emerging research also addresses the function of the urinary microbiota, including genetic factors associated with urinary tract colonization and interactions with uropathogens.

The urinary microbiome is a promising therapeutic target for urologic disease. However, a more functional understanding is necessary for the development of microbiome-based therapies. Future research should develop accurate animal models and explore functional relationships between the urinary microbiome and the host environment.
In silico
modelling of neuron signal impact of cytokine storm-induced demyelination
Authors: Adonias Geoflly L. , Siljak Harun , Balasubramaniam Sasitharan , Barros Michael Taynnan
Published: September 2024

In this study, we develop an
in silico
model of a neuron’s behaviour under demyelination caused by a cytokine storm to investigate the effects of viral infections in the brain. We use a comprehensive model to measure how cytokine-induced demyelination affects the propagation of action potential (AP) signals within a neuron. We analysed the effects of neuron-neuron communications by applying information and communication theory at different levels of demyelination. Our simulations demonstrate that virus-induced degeneration can play a role in the signal power and spiking rate, which compromise the propagation and processing of information between neurons. We propose a transfer function to model the weakening effects on the AP. Our results show that demyelination induced by a cytokine storm not only degrades the signal but also impairs its propagation within the axon. Our proposed
in silico
model can analyse virus-induced neurodegeneration and enhance our understanding of virus-induced demyelination.
Prevalence, patterns and predictors of paranormal beliefs in The Netherlands: a several-analysts approach
Authors: Hoogeveen S. , Borsboom D. , Kucharský Š. , Marsman M. , Molenaar D. , de Ron J. , Sekulovski N. , Visser I. , van Elk M. , Wagenmakers E.-J.
Published: September 2024

Paranormal beliefs encompass a wide variety of phenomena, including the existence of supernatural entities such as ghosts and witches, as well as extraordinary human abilities such as telepathy and clairvoyance. In the current study, we used a nationally representative sample (

N
=
2534

) to investigate the presence and correlates of paranormal beliefs among the secular Dutch population. The results indicated that most single paranormal phenomena (e.g. belief in clairvoyance) are endorsed by 10–20% of Dutch respondents; however, 55.6% of respondents qualify as paranormal believers based on the preregistered criterion that they believe in at least one phenomenon with considerable certainty. In addition, we invited four analysis teams with different methodological expertise to assess the structure of paranormal beliefs using traditional factor analysis, network analysis, Bayesian network analysis and latent class analysis (LCA). The teams’ analyses indicated adequate fit of a four-factor structure reported in a 1985 study, but also emphasized different conclusions across techniques; network analyses showed evidence against strong connectedness within most clusters, and suggested a five-cluster structure. The application of various analytic techniques painted a nuanced picture of paranormal beliefs and believers in The Netherlands and suggests that despite increased secularization, subgroups of the general population still believe in paranormal phenomena.
Deriving the cone fundamentals: a subspace intersection method
Authors: Wandell Brian A. , Goossens Thomas , Brainard David H.
Published: September 2024

Two ideas, proposed by Thomas Young and James Clerk Maxwell, form the foundations of colour science: (i) three types of retinal receptors encode light under daytime conditions, and (ii) colour matching experiments establish the critical spectral properties of this encoding. Experimental quantification of these ideas is used in international colour standards. However, for many years, the field did not reach consensus on the spectral properties of the biological substrate of colour matching: the spectral sensitivity of the cone fundamentals. By combining auxiliary data (thresholds, inert pigment analyses), complex calculations, and colour matching from genetically analysed dichromats, the human cone fundamentals have now been standardized. Here, we describe a new computational method to estimate the cone fundamentals using only colour matching from the three types of dichromatic observers. We show that it is not necessary to include data from trichromatic observers in the analysis or to know the primary lights used in the matching experiments. Remarkably, it is even possible to estimate the fundamentals by combining data from experiments using different, unknown primaries. We then suggest how the new method may be applied to colour management in modern image systems.
Amazonian rivers are leaky barriers to gene flow in forest understory birds
Authors: Weir Jason T. , Aleixo Alexandre , Pulido-Santacruz Paola
Published: September 2024

Ever since Alfred Russel Wallace’s nineteenth-century observation that related terrestrial species are often separated on opposing riverbanks, major Amazonian rivers have been recognized as key drivers of speciation. However, rivers are dynamic entities whose widths and courses may vary through time. It thus remains unknown how effective rivers are at reducing gene flow and promoting speciation over long timescales. We fit demographic models to genomic sequences to reconstruct the history of gene flow in three pairs of avian taxa fully separated by different Amazonian rivers, and whose geographic ranges do not make contact in headwater regions where rivers may cease to be barriers. Models with gene flow were best fit but still supported an initial period without any gene flow, which ranged from 187 000 to over 959 000 years, suggesting that rivers are capable of initiating speciation through long stretches of allopatric divergence. Allopatry was followed by either bursts or prolonged episodes of gene flow that retarded genomic differentiation but did not fully homogenize populations. Our results support Amazonian rivers as key barriers that promoted speciation and the build-up of species richness, but they also suggest that river barriers are often leaky, with genomic divergence accumulating slowly owing to episodes of substantial gene flow.
Inflammation and fibrinolysis in loiasis before and after ivermectin treatment: a biological pilot cross-sectional study
Authors: Lepage Tristan M. , Nzune-Toche Narcisse , Nkwengoua Lucie A. , Nana-Djeunga Hugues C. , Pion Sebastien D.S. , Kamgno Joseph , Boullé Charlotte , Campillo Jérémy T. , Boussinesq Michel , Tayou Claude T. , Chesnais Cédric B.
Published: September 2024

We assessed the impact of loiasis and its treatment with ivermectin on hemostasis and inflammation in 38 adults in Cameroon. Participants were divided into four balanced groups based on theirLoa loamicrofilarial densities. At baseline, a positive correlation was observed between microfilarial densities, neutrophils (p=0.012) and eosinophils (p<0.001). At day 4 following ivermectin administration, mean D-dimers significantly increased, from 725 ng/mL to 1,276 ng/mL (p=0.024). Mean eosinophils rose from 225/µL to 1,807/µL (p<0.001). C-reactive protein, fibrinogen, and alpha-1-globulin also increased significantly after treatment. Ivermectin treatment appeared to induce inflammation and pronounced fibrinolysis, indicative of coagulation activation.
Novel derivatives of BCV and (S)-HPMPA inhibit orthopoxviruses and human adenoviruses more potently than BCV
Authors: Zhang Yifan , Wan Yanmin , Guo Cuiyuan , Zhu Zhaoqin , Qiu Chao , Lu Jiasheng , Zhou Yanan , Zheng Jiaojiao , Dai Fahui , Cheng Xiaoyang , Deng Kunlu , Wang Wanhai , Wang Youchun , Zhang Wenhong
Published: September 2024

BCV and tecovirimat are the only two chemical drugs that have been approved to treat smallpox and can be requested for Mpox treatment through a single-patient Emergency Investigational New Drug (EIND) application. Disappointedly, the efficacy of tecovirimat manifested in a recent clinical trial is far from being satisfactory, while the clinical efficacy of BCV is still inconclusive. Given that MPXV, variola and other emerging orthopoxviruses are posing serious threats to global health, it is urgent to develop better therapeutics. In this study, we tested the antiviral effects of three novel prodrugs, which were designed based on previously reported parent drugs, either (S)-HPMPC (cidofovir) or (S)-HPMPA. We found that one of the (S)-HPMPA-based prodrugs, ODE-(S)-HPMPA formate, exhibited significantly better anti-orthopoxvirus activity than BCV both in vitro and in vivo, which also inhibited human adenovirus type 2 and type 21 more efficiently than BCV. Most strikingly, the EC50and EC90of ODE-(S)-HPMPA formate against MPXV were more than 40-fold lower than those of BCV. In contrast, we observed that the anti-HSV-1 activities of the (S)-HPMPA-based prodrugs were less effective than those of the cidofovir-based prodrugs (BCV and BCV formate), especially in vivo. Moreover, we showed for the first time that cytidine and adenine analog combined therapies could provide mice with complete protection against lethal challenges of both vaccinia and HSV-1. Collectively, we propose that both the ODE-(S)-HPMPA formate and the BCV/ODE-(S)-HPMPA formate combination are worth further investigations for their potential clinical applications.
Visual-Textual Integration in LLMs for Medical Diagnosis: A Quantitative Analysis
Authors: Agbareia Reem , Omar Mahmud , Soffer Shelly , Glicksberg Benjamin S , Nadkarni Girish N , Klang Eyal
Published: September 2024

Background and Aim

Visual data from images is essential for many medical diagnoses. This study evaluates the performance of multimodal Large Language Models (LLMs) in integrating textual and visual information for diagnostic purposes.

Methods

We tested GPT-4o and Claude Sonnet 3.5 on 120 clinical vignettes with and without accompanying images. Each vignette included patient demographics, a chief complaint, and relevant medical history. Vignettes were paired with either clinical or radiological images from two sources: 100 images from the OPENi database and 20 images from recent NEJM challenges, ensuring they were not in the LLMs’ training sets. Three primary care physicians served as a human benchmark. We analyzed diagnostic accuracy and the models’ explanations for a subset of cases.

Results

LLMs outperformed physicians in text-only scenarios (GPT-4o: 70.8%, Claude Sonnet 3.5: 59.5%, Physicians: 39.5%). With image integration, all improved, but physicians showed the largest gain (GPT-4o: 84.5%, p<0.001; Claude Sonnet 3.5: 67.3%, p=0.060; Physicians: 78.8%, p<0.001). LLMs changed their explanations in 45-60% of cases when presented with images, demonstrating some level of visual data integration.

Conclusion

Multimodal LLMs show promise in medical diagnosis, with improved performance when integrating visual evidence. However, this improvement is inconsistent and smaller compared to physicians, indicating a need for enhanced visual data processing in these models.
HBIcloud: An Integrative Multi-Omics Analysis Platform
Authors: He Shuang , Luo Yunqing , Dong Wei , Wang Wenquan , Chen Fei
Published: September 2024

As biological datasets have grown exponentially in size and complexity, there has been an increasing need for integrative tools that can handle diverse data types and facilitate comprehensive analyses. Traditional methods often require significant computational expertise, creating barriers for many researchers. HBIcloud is a comprehensive online platform designed to facilitate multi-omics data analysis by integrating a wide array of tools across genomics, transcriptomics, proteomics, metabolomics, phenomics, and multi-omics integration. Developed to address the growing complexity and volume of biological data, HBIcloud provides researchers with a powerful and user-friendly resource for conducting sophisticated analyses without the need for extensive programming skills. With a total of 94 tools, the platform offers standardized workflows, extensive parameter options, and rich documentation, catering to the diverse needs of the scientific community. The research behind HBIcloud aimed to create a centralized, user-friendly platform that simplifies the analytical process, enabling researchers to focus on scientific discovery rather than technical challenges. By integrating a wide array of tools and offering extensive support and documentation, HBIcloud addresses the critical need for standardized, reproducible workflows in multi-omics research. This paper presents a detailed overview of HBIcloud, highlighting its development background, key features, and its significant contribution to advancing multi-omics research. Furthermore, we discuss the future prospects of HBIcloud, including planned enhancements and its potential for high citation impact within the scientific community. By providing a robust and versatile platform, HBIcloud aims to accelerate discovery and innovation in the field of multi-omics, fostering collaborative research and expanding the boundaries of biological understanding. The official website of HBIcloud ishttps://bioinformatics.hainanu.edu.cn/HBIcloud/.
Structured Clinical Reasoning Prompt Enhances LLM’s Diagnostic Capabilities in Diagnosis Please Quiz Cases
Authors: Sonoda Yuki , Kurokawa Ryo , Hagiwara Akifumi , Asari Yusuke , Fukushima Takahiro , Kanzawa Jun , Gonoi Wataru , Abe Osamu
Published: September 2024

Background

Large Language Models (LLMs) show promise in medical diagnosis, but their performance varies with prompting. Recent studies suggest that modifying prompts may enhance diagnostic capabilities.

Objective

This study aimed to test whether a prompting approach that aligns with general clinical reasoning methodology—specifically, separating processes of summarizing clinical information and making diagnoses based on the summary instead of one-step processing—can enhance LLM’s medical diagnostic capabilities

Methods

322 quiz questions fromRadiology’sDiagnosis Please cases (1998-2023) were used. We employed Claude 3.5 Sonnet, a state-of-the-art LLM, to compare three approaches: 1) Conventional zero-shot chain-of-thought prompt, as a baseline, 2) two-step approach: LLM organizes patient history and imaging findings, then provides diagnoses, and 3) Summary-only approach: Using only the LLM-generated summary for diagnoses.

Results

The two-step approach significantly outperformed both baseline and summary-only methods in diagnosis accuracy, as determined by McNemar tests. Primary diagnosis accuracy was 60.6% for the two-step approach, compared to 56.5% for baseline (p=0.042) and 56.3% for summary-only (p=0.035). For the top three diagnoses, accuracy was 70.5%, 66.5%, and 65.5% respectively (p=0.005 for baseline, p=0.008 for summary-only). No significant differences were observed between baseline and summary-only approaches.

Conclusion

Our results indicate that a structured clinical reasoning approach enhances LLM’s diagnostic accuracy. This method shows potential as a valuable tool for deriving diagnoses from free-text clinical information. The approach aligns well with established clinical reasoning processes, suggesting its potential applicability in real-world clinical settings.
Interpretable scRNA-seq Analysis with Intelligent Gene Selection
Authors: Ni Tianhao , Zhang Xinyu , Jin Kaixiu , Pei Guanxiong , Xue Nan , Yan Guanao , Li Taihao , Li Bingjie
Published: September 2024

Abstract

Single-cell RNA sequencing (scRNA-seq) data analysis faces multiple challenges, including high dimensionality, significant noise, and data loss. To effectively address these issues, we introduce AIGS, a robust and transparent single-cell analysis framework. AIGS utilizes an intelligent gene selection method that systematically identifies the most informative genes for clustering based on the normalized mutual information between pre-learned pseudo-labels and quantified genes. Additionally, AIGS incorporates a scale-invariant distance metric to assess cell-to-cell similarity, enhancing connections between homogenous cells and ensuring more accurate and robust results. Through comprehensive comparisons with state-of-the-art techniques, AIGS demonstrates superior performance in both clustering accuracy and multi-resolution visualization quality. Our in-depth analysis of clustering and visualization results further reveals that AIGS can uncover complex, stage-specific gene expression patterns during the same developmental cell stage.
Urine cf-Nucleosomes: A Non-invasive Window into Human Physiology and Disease
Authors: Lotem Matan , Sharkia Israa , Azria Batia , Falik-Michaeli Tal , Friedman Nir
Published: September 2024

Urine contains fragments of cell-free DNA, which hold valuable molecular insights into the processes occurring within the urinary system and the whole body. It is unknown whether these fragments are in the form of chromatin, as in the cell of origin, and whether they maintain the cell of origin chromatin modifications. Here, we examine these questions using cell-free chromatin immunoprecipitation followed by sequencing (cfChIP-seq) on human urine. We demonstrate that we can capture cell-free nucleosomes (cf-nucleosomes) from urine and that these preserve multiple histone post-translational modifications indicative of activation and repression. By analyzing these modifications, we identified the primary tissues contributing to cf-nucleosomes in a cohort of healthy individuals. Notably, we observe distinct populations of circulating cf-nucleosomes in urine samples from healthy donors with a contribution from the kidney, which are not detected in matched urine exfoliated cells or matching plasma samples. We further show that, at most, a negligible amount of urine cf-nucleosomes originates from plasma, suggesting that kidney filtration excludes plasma-circulating nucleosomes from urine. Additionally, we show that urine cf nucleosomes can report pathologically driven changes in the urine of bladder cancer patients, reflecting tumor-associated transcriptional programs and immune responses. Our findings highlight the potential of urine cf nucleosomes as accessible, noninvasive biomarkers for both basic research in renal physiology and monitoring urinary pathologies.

Key Findings

Urine cell-free nucleosomes exist and retain multiple histone marks that are informative of gene promoters and enhancers.

Urine cfChIP-seq identifies bladder, kidney, and immune cells as the major contributing organs to the pool of urine cell-free nucleosomes.

The populations of cell-free nucleosomes in urine and blood are distinct and primarily disjoint, suggesting that few, if any, nucleosomes cross the blood-urine interface.

Urine cell-free nucleosomes reflect pathologically driven changes in tumors and immune cells responding to the tumor.
Enhancing student comprehension of paternity assignment in molecular primatology: a pilot study using a Shiny web application in Kenya
Authors: Mwaura David Kiragu , Anderson Jordan A , Kiboi Daniel , Akinyi Mercy Y , Tung Jenny
Published: September 2024

Kinship is a major determinant of affiliative and mating behavior in primates. In field studies, identifying kin typically relies in part on genetic analysis, especially for discriminating paternal relationships. Such analyses assume knowledge of Mendelian inheritance, genotyping technologies, and basic statistical inference. Consequently, they can be difficult for students to grasp, particularly through traditional lecture formats. Here, we investigate whether integrating an additional active learning approach--interaction with a Shiny web application, DadApp, which implements a popular paternity inference approach in an accessible graphical user interface--improves student understanding of genetic kinship analysis in molecular primatology. We do so in the context of a non-traditional learning environment in Kenya, a developing nation in which students have limited access to technology, and where the efficacy of educational Shiny apps has never been assessed. Twenty-eight (28) participants with diverse educational backgrounds attended an introductory lecture on genetics and paternity inference, completed a pre-test, interacted with DadApp via a structured set of exercises and questions, and then completed a post-test and survey about their experience and subjective understanding. Post-test scores significantly improved relative to pre-test scores (p-value=3.75 x 10-6). Further, student interest and confidence in the subject matter significantly increased after the practical session with DadApp. Our results suggest that Shiny web app-based active learning approaches have potential benefits in communicating complex topics in molecular primatology, including in resource-limited settings where such methods have not yet experienced high penetrance.