bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disentangling the acute subjective effects of classic psychedelics from their enduring therapeutic properties
Authors: Atiq Mazen A. , Baker Matthew R. , Voort Jennifer L. Vande , Vargas Maxemiliano V. , Choi Doo-Sup 
Published: May 2024

AbstractRecent research with classic psychedelics suggests significant therapeutic potential, particularly for neuropsychiatric disorders. A mediating influence behind symptom resolution is thought to be the personal insight – at times, bordering on the mystical – one acquires during the acute phase of a psychedelic session. Indeed, current clinical trials have found strong correlations between the acute subjective effects (ASE) under the influence of psychedelics and their enduring therapeutic properties. However, with potential barriers to widespread clinical implementation, including the healthcare resource-intensive nature of psychedelic sessions and the exclusion of certain at-risk patient groups, there is an active search to determine whether ASE elimination can be accompanied by the retention of persisting therapeutic benefits of these class of compounds. Recognizing the aberrant underlying neural circuitry that characterizes a range of neuropsychiatric disorders, and that classic psychedelics promote neuroplastic changes that may correct abnormal circuitry, investigators are rushing to design and discover compounds with psychoplastogenic, but not hallucinogenic (i.e., ASE), therapeutic potential. These efforts have paved the discovery of ‘non-psychedelic/subjective psychedelics’, or compounds that lack hallucinogenic activity but with therapeutic efficacy in preclinical models. This review aims to distill the current evidence – both clinical and preclinical – surrounding the question: can the ASE of classic psychedelics be dissociated from their sustained therapeutic properties? Several plausible clinical scenarios are then proposed to offer clarity on and potentially answer this question.
Modular Invariance of (Logarithmic) Intertwining Operators
Authors: Huang Yi-Zhi 
Published: May 2024

AbstractLet V be a $$C_2$$

C
2

-cofinite vertex operator algebra without nonzero elements of negative weights. We prove the conjecture that the spaces spanned by analytic extensions of pseudo-q-traces ($$q=e^{2\pi i\tau }$$

q
=

e

2
π
i
τ

) shifted by $$-\frac{c}{24}$$

-

c
24

of products of geometrically-modified (logarithmic) intertwining operators among grading-restricted generalized V-modules are invariant under modular transformations. The convergence and analytic extension result needed to formulate this conjecture and some consequences on such shifted pseudo-q-traces were proved by Fiordalisi (Logarithmic intertwining operator and genus-one correlation functions, 2015) and Fiordalisi (Commun Contemp Math 18:1650026, 2016) using the method developed in Huang (Commun Contemp Math 7:649–706, 2005). The method that we use to prove this conjecture is based on the theory of the associative algebras $$A^{N}(V)$$

A
N

(
V
)

for $$N\in \mathbb {N}$$

N
∈
N

, their graded modules and their bimodules introduced and studied by the author in Huang (Associative algebras and the representation theory of grading-restricted vertex algebras, 2020) and Huang (Commun Math Phys 396:1–44, 2022). This modular invariance result gives a construction of $$C_2$$

C
2

-cofinite genus-one logarithmic conformal field theories from the corresponding genus-zero logarithmic conformal field theories.
Genetic Prediction of Osteoporosis by Anti-Müllerian Hormone Levels and Reproductive Factors in Women: A Mendelian Randomization Study
Authors: Li Yuan , Lai Jinquan , Wu Wenbo , Ling Shuyi , Dai Yuqing , Zhong Zhisheng , Chen Xiaodong , Zheng Yuehui 
Published: May 2024

AbstractPrevious observational studies have suggested that anti-Müllerian hormone (AMH) and reproductive factors are linked to reduced bone mineral density (BMD) and an increased risk of osteoporosis (OP) in women. However, related studies are limited, and these traditional observational studies may be subject to residual confounders and reverse causation, while also lacking a more comprehensive observation of various reproductive factors. Univariate and multivariate two-sample Mendelian randomization analyses were conducted to determine the causal associations of AMH levels and six reproductive factors with BMD and OP, using the random-effects inverse-variance weighted method. Heterogeneity was assessed using Cochran’s Q-statistic, and sensitivity analyses were performed to identify causal correlations. Age at menarche (AAM) was negatively associated with total body BMD (TB-BMD) in females aged 45–60 and over 60 years, as well as with heel bone mineral density (eBMD). Conversely, age at natural menopause (ANM) was positively associated with TB-BMD in the same age ranges and with eBMD. ANM was only causally associated with self-reported OP and showed no significant correlation with definitively diagnosed OP. Neither AMH level nor other reproductive factors were significantly associated with a genetic predisposition to BMD at any age and OP. Later AAM and earlier ANM are significantly genetically causally associated with decreased BMD but not with OP. AMH levels, length of menstrual cycle, age at first birth, age at last birth, and number of live births, in terms of genetic backgrounds, are not causally related to BMD or OP.
Investigation of Fungal Community Structure in the Gut of the Stag Beetle Dorcus hopei (Coleoptera; Lucanidae): Comparisons Among Developmental Stages
Authors: Bin Xiaoyan , Wang Pan , Shen Yagang , Xiang Xingjia , Jafir Muhammad , Wan Xia 
Published: May 2024

AbstractStag beetles, recognized as common saproxylic insects, are valued for their vibrant coloration and distinctive morphology. These beetles play a crucial ecological role in decomposition and nutrient cycling, serving as a vital functional component in ecosystem functioning. Although previous studies have confirmed that stag beetles are predominantly fungivores, the fluctuations in their intestinal fungal communities at different developmental stages remain poorly understood. In the current study, high-throughput sequencing was employed to investigate the dynamic changes within intestinal fungal communities at various developmental stages in the stag beetle Dorcus hopei. Results showed that microbial diversity was higher during the larval stage than during the pupal and adult stages. Furthermore, significant differences were identified in the composition of the intestinal fungal communities across the larval, pupal, and adult stages, suggesting that developmental transitions may be crucial factors contributing to variations in fungal community composition and diversity. Dominant genera included Candida, Scheffersomyces, Phaeoacremonium, and Trichosporon. Functional predictions indicated a greater diversity and relative abundance of endosymbiotic fungi in the larval gut, suggesting a potential dependency of larvae on beneficial gut fungi for nutrient acquisition. Additionally, the application of abundance-based β-null deviation and niche width analyses revealed that the adult gut exerted a stronger selection pressure on its fungal community, favoring certain taxa. This selection process culminates in a more robust co-occurrence network of fungal communities within the adult gut, thereby enhancing their adaptability to environmental fluctuations. This study advances our understanding of the intestinal fungal community structure in stag beetles, providing a crucial theoretical foundation for the development of saproxylic beetle resources, biomass energy utilization, plastic degradation strategies, and beetle conservation efforts.
Investigation of controlled salmeterol xinafoate and fluticasone propionate release from double molecular imprinted nanoparticles
Authors: Feyzioğlu-Demir Esra , Akgöl Sinan 
Published: May 2024

AbstractSalmeterol xinafoate (SAM) and fluticasone propionate (FLU) are one of the drug combinations used together in the treatment of lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). The aim of this study is to investigate the usability of novel dual molecular imprinted nanoparticles (poly(2-hydroxyethyl methacrylate-N-methacryloyl-(L)-alanine-N-methacryloyl-(L)-histidine) [p(HEMA-MAAL-MAH)], abbr. DMIPNPs) as a controlled drug release systems. In this study, SAM and FLU drugs were chosen as model drugs because they are used in the treatment of these diseases. DMIPNPs were prepared by surfactant-free emulsion polymerization method and characterized by scanning electron microscopy (SEM) and fourier transform infrared spectrometer (FTIR). In in vitro drug release experiments, drug release conditions were optimized. SAM and FLU release from DMIPNPs experiments were also performed in the simulated lung fluid (SLF). The amount of released SAM and FLU were found as 4.79 and 5.68 mg/g in the SLF medium at the end of 48 h, respectively. The release kinetics of SAM and FLU from DMIPNPs were calculated in the SLF medium. The release of SAM and FLU was determined to be compatible with the Higuchi release models. According to these results, these DMIPNPs, dual-template molecular imprinted nanoparticles with dual monomers, are promising materials that can be used in the controlled release of two different drugs.
Graphical abstract
The role of the Golden2-like (GLK) transcription factor in regulating terpenoid indole alkaloid biosynthesis in Catharanthus roseus
Authors: Cole-Osborn Lauren F. , McCallan Shannon A. , Prifti Olga , Abu Rafay , Sjoelund Virginie , Lee-Parsons Carolyn W. T. 
Published: May 2024

Abstract
Key message
A GLK homologue was identified and functionally characterized in Catharanthus roseus. Silencing CrGLK with VIGS or the chloroplast retrograde signaling inducer lincomycin increased terpenoid indole alkaloid biosynthesis.

Abstract
Catharanthus roseus is the sole source of the chemotherapeutic terpenoid indole alkaloids (TIAs) vinblastine and vincristine. TIA pathway genes, particularly genes in the vindoline pathway, are expressed at higher levels in immature versus mature leaves, but the molecular mechanisms responsible for this developmental regulation are unknown. We investigated the role of GOLDEN2-LIKE (GLK) transcription factors in contributing to this ontogenetic regulation since GLKs are active in seedlings upon light exposure and in the leaf’s early development, but their activity is repressed as leaves age and senesce.
We identified a GLK homologue in C. roseus and functionally characterized its role in regulating TIA biosynthesis, with a focus on the vindoline pathway, by transiently reducing its expression through two separate methods: virus-induced gene silencing (VIGS) and application of chloroplast retrograde signaling inducers, norflurazon and lincomycin. Reducing CrGLK levels with each method reduced chlorophyll accumulation and the expression of the light harvesting complex subunit (LHCB2.2), confirming its functional homology with GLKs in other plant species. In contrast, reducing CrGLK via VIGS or lincomycin increased TIA accumulation and TIA pathway gene expression, suggesting that CrGLK may repress TIA biosynthesis. However, norflurazon had no effect on TIA gene expression, indicating that reducing CrGLK alone is not sufficient to induce TIA biosynthesis. Future work is needed to clarify the specific molecular mechanisms leading to increased TIA biosynthesis with CrGLK silencing. This is the first identification and characterization of GLK in C. roseus and the first investigation of how chloroplast retrograde signaling might regulate TIA biosynthesis.
Comprehensive evaluation of vaginal intraepithelial neoplasia development after hysterectomy: insights into diagnosis and treatment strategies
Authors: Wei Jiahui , Wu Yumei 
Published: May 2024

AbstractVaginal intraepithelial neoplasia (VaIN), a precancerous lesion associated with human papillomavirus (HPV), impacts women’s health and quality of life. However, the natural progression of VaIN after hysterectomy remains uncertain, due to its low incidence. The existing literature predominantly consists of single-center retrospective studies lacking robust evidence-based medicine. The management of VaIN after hysterectomy is diverse and controversial, lacking a consensus on the optimal approach. Therefore, it is imperative to investigate the development of VaIN after hysterectomy, emphasizing the importance of accurate diagnosis and effective management strategies.
Regional hippocampal atrophy reflects memory impairment in patients with early relapsing remitting multiple sclerosis
Authors: Cortese Rosa , Battaglini Marco , Stromillo Maria Laura , Luchetti Ludovico , Leoncini Matteo , Gentile Giordano , Gasparini Daniele , Plantone Domenico , Altieri Manuela , D’Ambrosio Alessandro , Gallo Antonio , Giannì Costanza , Piervincenzi Claudia , Pantano Patrizia , Pagani Elisabetta , Valsasina Paola , Preziosa Paolo , Tedone Nicolo’ , Rocca Maria Assunta , Filippi Massimo , De Stefano Nicola ,   INNI Network, Bisecco Alvino , Esposito Fabrizio , De Rosa Alessandro , Ruggieri Serena , Tommasin Silvia , Petsas Nikolaos , Storelli Loredana , Sala Stefania 
Published: May 2024

Abstract
Background
Research work has shown that hippocampal subfields are atrophic to varying extents in multiple sclerosis (MS) patients. However, studies examining the functional implications of subfield-specific hippocampal damage in early MS are limited. We aim to gain insights into the relationship between hippocampal atrophy and memory function by investigating the correlation between global and regional hippocampal atrophy and memory performance in early MS patients.

Methods
From the Italian Neuroimaging Network Initiative (INNI) dataset, we selected 3D-T1-weighted brain MRIs of 219 early relapsing remitting (RR)MS and 246 healthy controls (HC) to identify hippocampal atrophic areas. At the time of MRI, patients underwent Selective-Reminding-Test (SRT) and Spatial-Recall-Test (SPART) and were classified as mildly (MMI-MS: n.110) or severely (SMI-MS: n:109) memory impaired, according to recently proposed cognitive phenotypes.

Results
Early RRMS showed lower hippocampal volumes compared to HC (p < 0.001), while these did not differ between MMI-MS and SMI-MS. In MMI-MS, lower hippocampal volumes correlated with worse memory tests (r = 0.23–0.37, p ≤ 0.01). Atrophic voxels were diffuse in the hippocampus but more prevalent in cornu ammonis (CA, 79%) than in tail (21%). In MMI-MS, decreased subfield volumes correlated with decreases in memory, particularly in the right CA1 (SRT-recall: r = 0.38; SPART: r = 0.34, p < 0.01). No correlations were found in the SMI-MS group.

Conclusion
Hippocampal atrophy spreads from CA to tail from early disease stages. Subfield hippocampal atrophy is associated with memory impairment in MMI-MS, while this correlation is lost in SMI-MS. This plays in favor of a limited capacity for an adaptive functional reorganization of the hippocampi in MS patients.
Melatonin and mesenchymal stem cells co-administration alleviates chronic obstructive pulmonary disease via modulation of angiogenesis at the vascular-alveolar unit
Authors: Hanna Mira , Elnassag Sabreen Sayed , Mohamed Dina Hisham , Elbaset Marawan Abd , Shaker Olfat , Khowailed Effat A. , Gouda Sarah Ali Abdelhameed 
Published: May 2024

AbstractChronic obstructive pulmonary disease (COPD) is considered a severe disease mitigating lung physiological functions with high mortality outcomes, insufficient therapy, and pathophysiology pathways which is still not fully understood. Mesenchymal stem cells (MSCs) derived from bone marrow play an important role in improving the function of organs suffering inflammation, oxidative stress, and immune reaction. It might also play a role in regenerative medicine, but that is still questionable. Additionally, Melatonin with its known antioxidative and anti-inflammatory impact is attracting attention nowadays as a useful treatment. We hypothesized that Melatonin may augment the effect of MSCs at the level of angiogenesis in COPD. In our study, the COPD model was established using cigarette smoking and lipopolysaccharide. The COPD rats were divided into four groups: COPD group, Melatonin-treated group, MSC-treated group, and combined treated group (Melatonin–MSCs). We found that COPD was accompanied by deterioration of pulmonary function tests in response to expiratory parameter affection more than inspiratory ones. This was associated with increased Hypoxia inducible factor-1α expression and vascular endothelial growth factor level. Consequently, there was increased CD31 expression indicating increased angiogenesis with massive enlargement of airspaces and thinning of alveolar septa with decreased mean radial alveolar count, in addition to, inflammatory cell infiltration and disruption of the bronchiolar epithelial wall with loss of cilia and blood vessel wall thickening. These findings were improved significantly when Melatonin and bone marrow-derived MSCs were used as a combined treatment proving the hypothesized target that Melatonin might augment MSCs aiming at vascular changes.
Distribution of pathogenic variants in the CFTR gene in a representative cohort of people with cystic fibrosis in the Kingdom of Bahrain
Authors: Majed Osama A. Karim , Majed Fatema Osama , Almoamen Nabeel Jasim , Alsatrawi Husain Baqer , Shehabi Salma Dawood , Hrbková Jana , Libik Malgorzata , Macek Milan 
Published: May 2024

Abstract
Background
Cystic fibrosis (CF) is a rare multi-systemic recessive disorder. The spectrum and the frequencies of CFTR mutations causing CF vary amongst different populations in Europe and the Middle East. In this study, we characterised the distribution of CF-causing mutations (i.e. pathogenic variants in the CFTR gene) in a representative CF cohort from the Kingdom of Bahrain based on a three-decade-long analysis at a single tertiary centre. We aim to improve CF genetic diagnostics, introduce of CF neonatal screening and provide CFTR modulator therapy (CFTRm).

Methods
CFTR genotyping and associated clinical information were drawn from a longitudinal cohort. We sequenced 56 people with CF (pwCF) that had one or both CFTR mutations unidentified and carried out comprehensive bioinformatic- and family-based segregation analyses of detected variants, including genotype–phenotype correlations and disease incidence estimates. The study methodology could serve as a basis for other non-European CF populations with a high degree of consanguinity.

Results
Altogether 18 CF-causing mutations were identified, 15 of which were not previously detected in Bahrain, accounting for close to 100% of all population-specific alleles. The most common alleles comprise c.1911delG [2043delG; 22.8%], c.2988+1G > A [3120+1G>A; 16.3%], c.2989-1G>A [3121-1G>A; 14.1%], c.3909C>G [N1303K; 13.0%], and c.1521_1523delCTT [p.PheF508del; 7.6%]. Although the proportion of 1st cousin marriages has decreased to 50%, the frequency of homozygosity in our pwCF is 67.4%, thereby indicating that CF still occurs in large, often related, families. pwCF in Bahrain present with faltering growth, pancreatic insufficiency and classical sino-pulmonary manifestations. Interestingly, two pwCF also suffer from sickle cell disease. The estimated incidence of CF in Bahrain based on data from the last three decades is 1 in 9,880 live births.

Conclusion
The most commonCF-causing mutations in Bahraini pwCF were identified, enabling more precise diagnosis, introduction of two-tier neonatal screening and fostering administration of CFTRm.
Clinical outcomes of posterior fossa arteriovenous malformations: a single center experience
Authors: Miron Ioana , Prună Viorel M. , Visarion Dan , Giovani Andrei , Sandu Aurelia M. , Brehar Felix M. , Petrescu George E. D. , Gorgan Radu M. 
Published: May 2024

Abstract

Background
Posterior fossa arterio-venous malformations (pfAVMs) are challenging lesions due to the anatomical particularities of the posterior fossa, and the high incidence of hemorrhagic presentation. The two most important goals when treating AVMs are preserving neurological function and preventing rupture, or a second hemorrhage. The aim of this study was to analyze the clinical and imaging features of pfAVMs to identify the factors that influence the prognosis of these patients.

Methods
We conducted a single-center retrospective observational study that included patients treated at our institution with pfAVMs between January 1997 and December 2021.

Results
A total of 48 patients were included. A good modified Rankin score (mRS) was observed in 33 cases (69%) at presentation. Thirty-four patients (71%) presented with a ruptured AVM. Out of these, 19 patients (40%) had intraventricular hemorrhage. Microsurgical resection was performed in 33 cases (69%), while in the other cases, the patients opted for conservative management (7 cases, 15%), stereotactic radiosurgery (SRS) (6 cases, 12%), or endovascular treatment (2 cases, 4%). Patients ≤ 30 years old were more prone to hemorrhagic presentation (OR: 5.23; 95% CI: 1.42–17.19; p = 0.024) and this remained an independent risk factor for rupture after multivariate analysis as well (OR: 4.81; 95% CI: 1.07–21.53; p = 0.040). Following multivariate analysis, the only factor independently associated with poor prognosis in the surgically treated subgroup was a poor clinical status (mRS 3–5) at admission (OR: 96.14; 95% CI: 5.15–1793.9; p = 0.002).

Conclusions
Management of posterior fossa AVMs is challenging, and patients who present with ruptured AVMs often have a poor clinical status at admission leading to a poor prognosis. Therefore, proper and timely management of these patients is essential.
A systematic review and meta-analysis of the prevalence and global distribution of middle mesial canals in mandibular molars identified by CBCT
Authors: Motamedi Mahmood Reza Kalantar , Amirzade-Iranaq Mohammad Hosein , Ha William N. 
Published: May 2024

Abstract
Objectives
This systematic review and meta-analysis aimed to evaluate the prevalence of middle mesial canal (MMC) in permanent mandibular molars of different populations and regions based on cone-beam computed tomography (CBCT) studies.

Materials and methods
PubMed, Scopus, Embase, Web of Science, and Open-Grey were searched up to October 2023 according to specific keywords. A hand search was conducted on the references of the included studies and articles from three peer-reviewed journals in endodontics. The main variable of interest was the prevalence of MMC. Additional data such as the total number of included cases, age and country of the population, CBCT device information, voxel size, and field of view details were also extracted. Extracted data were analyzed qualitatively with the JBI quality assessment checklist and quantitatively with STATA software.

Results
Of 32,793 studied teeth, the cumulative prevalence of MMC in both mandibular 1st and 2nd molars was 3.11% (95% CI: 2.00-4.44%). The subgroup analysis reveals a prevalence of 4.15% (95% CI: 2.69-5.89%) for mandibular 1st molars and 1.2% (95% CI: 0.2-2.83%) for mandibular 2nd molars. The highest prevalence of MMC in 1st molar was attributed to South Asia (11.24%) and Africa (6.61%).

Conclusions
The prevalence of MMC varies among regions. Clinicians should be aware of the potential prevalence of MMC, particularly in mandibular first molars, as a missed MMC could result in endodontic failure.

Clinical relevance
The presence of MMCs varies in different geographic regions (0% to 29.7%). Clinicians should always look for MMC when doing an endodontic treatment on mandibular molars, as the presence of this canal is not uncommon. We suggest searching for this canal as if searching for the second mesiobuccal canal of maxillary 1st molars.