bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cortical inhibition in neurofibromatosis type 1 is modulated by lovastatin, as demonstrated by a randomized, triple-blind, placebo-controlled clinical trial
Authors: Bernardino Inês , Dionísio Ana , Castelo-Branco Miguel 
Published: August 2022

AbstractNeurofibromatosis type 1 (NF1) is associated with GABAergic dysfunction which has been suggested as the underlying cause of cognitive impairments. Previous intervention trials investigated the statins’ effects using cognitive outcome measures. However, available outcome measures have led to inconclusive results and there is a need to identify other options. Here, we aimed at investigating alternative outcome measures in a feasibility trial targeting cortical inhibition mechanisms known to be altered in NF1. We explored the neurochemical and physiological changes elicited by lovastatin, with magnetic resonance spectroscopy and transcranial magnetic stimulation (TMS). Fifteen NF1 adults participated in this randomized, triple-blind, placebo-controlled crossover trial (Clinicaltrials.gov NCT03826940) composed of one baseline and two reassessment visits after lovastatin/placebo intake (60 mg/day, 3-days). Motor cortex GABA+ and Glx concentrations were measured using HERMES and PRESS sequences, respectively. Cortical inhibition was investigated by paired-pulse, input–output curve, and cortical silent period (CSP) TMS protocols. CSP ratios were significantly increased by lovastatin (relative: p = 0.027; absolute: p = 0.034) but not by placebo. CSP durations showed a negative correlation with the LICI 50 ms amplitude ratio. Lovastatin was able to modulate cortical inhibition in NF1, as assessed by TMS CSP ratios. The link between this modulation of cortical inhibition and clinical improvements should be addressed by future large-scale studies.
Impact of habitual chewing on gut motility via microbiota transition
Authors: Yaoita Fukie , Watanabe Keita , Kimura Ikuo , Miyazawa Masayuki , Tsuchiya Shinobu , Kanzaki Makoto , Tsuchiya Masahiro , Tan-No Koichi 
Published: August 2022

AbstractThe gut environment, including the microbiota and its metabolites and short-chain fatty acids (SCFA), is essential for health maintenance. It is considered that functional recovery treatment for masticatory dysphagia affects the composition of the gut microbiota, indicating that habitual mastication, depending on the hardness of the food, may affect the gut microbiota and environment. However, the impact of chronic powdered diet feeding on the colonic condition and motility remains unclear. Here, we evaluated various colonic features in mice fed with powdered diets for a long-term and a mouse model with masticatory behavior. We observed a decreased abundance of the SCFA-producing bacterial genera in the ceca of the powdered diet-fed mice. Based on the importance of SCFAs in gut immune homeostasis and motility, interestingly, powdered diet feeding also resulted in constipation-like symptoms due to mild colitis, which were ameliorated by the administration of a neutrophil-depleting agent and neutrophil elastase inhibitors. Lastly, the suppressed colonic motility in the powdered diet-fed mice was significantly improved by loading masticatory activity for 2 h. Thus, feeding habits with appropriate masticatory activity and stimulation may play a key role in providing a favorable gut environment based on interactions between the gut microbiota and host immune system.
The Mis6 inner kinetochore subcomplex maintains CENP-A nucleosomes against centromeric non-coding transcription during mitosis
Authors: Hirai Hayato , Shogaki Yuki , Sato Masamitsu 
Published: August 2022

AbstractCentromeres are established by nucleosomes containing the histone H3 variant CENP-A. CENP-A is recruited to centromeres by the Mis18–HJURP machinery. During mitosis, CENP-A recruitment ceases, implying the necessity of CENP-A maintenance at centromeres, although the exact underlying mechanism remains elusive. Herein, we show that the inner kinetochore protein Mis6 (CENP-I) and Mis15 (CENP-N) retain CENP-A during mitosis in fission yeast. Eliminating Mis6 or Mis15 during mitosis caused immediate loss of pre-existing CENP-A at centromeres. CENP-A loss occurred due to the transcriptional upregulation of non-coding RNAs at the central core region of centromeres, as confirmed by the observation RNA polymerase II inhibition preventing CENP-A loss from centromeres in the mis6 mutant. Thus, we concluded that the inner kinetochore complex containing Mis6–Mis15 blocks the indiscriminate transcription of non-coding RNAs at the core centromere, thereby retaining the epigenetic inheritance of CENP-A during mitosis.
An inhibited laser
Authors: Shi Tiantian , Pan Duo , Chen Jingbiao 
Published: August 2022

AbstractTraditional lasers function using resonant cavities, in which the round-trip optical path is equal to an integer multiple of the intracavity wavelengths to constructively enhance the spontaneous emission rate. Taking advantage of the cavity enhancement effect, the narrowest sub-10-mHz-linewidth laser and a 10−16-fractional-frequency-stability superradiant active optical clock (AOC) have been achieved. However, a laser with atomic spontaneous radiation being destructively inhibited in an anti-resonant cavity, where the atomic resonance is exactly between two adjacent cavity resonances, has not been reported. Herein, we experimentally demonstrate the inhibited laser. Compared with traditional AOCs, which exhibit superiority in terms of the high suppression of cavity noise, the suppression of the cavity-pulling effect of an inhibited laser can be further improved by a factor of$${\left(2{{{{{{{\mathcal{F}}}}}}}}/\pi \right)}^{2}$$2F/π2, which is improved from 26 to 53 times. This study will guide further development of AOCs with better stability, and thus, it is significant for quantum metrology and may lead to new research in the laser physics and cavity quantum electrodynamics fields.
Enzymatic upgrading of nanochitin using an ancient lytic polysaccharide monooxygenase
Authors: Barandiaran Leire , Alonso-Lerma Borja , Reifs Antonio , Larraza Izaskun , Olmos-Juste Raquel , Fernandez-Calvo Alba , Jabalera Ylenia , Eceiza Arantxa , Perez-Jimenez Raul 
Published: August 2022

AbstractNumerous enzymes have the potential to upgrade biomass, converting it into high-tech materials for new applications. However, the features of natural enzymes often limit their use beyond chemical conversion of the substrate. The development of strategies for the enzymatic conversion of biomass into high-value materials may broaden the range of applications of enzymes and enzyme design techniques. A relevant case is lytic polysaccharide monooxygenase (LPMO), a class of enzymes that catalyzes the oxidative cleavage of glycosidic bonds. Here, we show that an ancestral LPMO can generate chitin nanocrystals. Physicochemical characterization of the chitin nanocrystals demonstrates modifications that make it superior compared to chitin obtained by chemical treatments. We show that the nanocrystals are suitable for controlled 2D and 3D cell cultures, as well as for engineering a biomatrix that combines with graphene oxide, forming a hybrid conductive bioink.
Nuclear morphology is a deep learning biomarker of cellular senescence
Authors: Heckenbach Indra , Mkrtchyan Garik V. , Ezra Michael Ben , Bakula Daniela , Madsen Jakob Sture , Nielsen Malte Hasle , Oró Denise , Osborne Brenna , Covarrubias Anthony J , Idda M. Laura , Gorospe Myriam , Mortensen Laust , Verdin Eric , Westendorp Rudi , Scheibye-Knudsen Morten 
Published: August 2022

AbstractCellular senescence is an important factor in aging and many age-related diseases, but understanding its role in health is challenging due to the lack of exclusive or universal markers. Using neural networks, we predict senescence from the nuclear morphology of human fibroblasts with up to 95% accuracy, and investigate murine astrocytes, murine neurons, and fibroblasts with premature aging in culture. After generalizing our approach, the predictor recognizes higher rates of senescence in p21-positive and ethynyl-2’-deoxyuridine (EdU)-negative nuclei in tissues and shows an increasing rate of senescent cells with age in H&E-stained murine liver tissue and human dermal biopsies. Evaluating medical records reveals that higher rates of senescent cells correspond to decreased rates of malignant neoplasms and increased rates of osteoporosis, osteoarthritis, hypertension and cerebral infarction. In sum, we show that morphological alterations of the nucleus can serve as a deep learning predictor of senescence that is applicable across tissues and species and is associated with health outcomes in humans.
Catalytic Dienylation: An Emergent Strategy for the Stereoselective Construction of Conjugated Dienes and Polyenes
Authors: Ahmed Jasimuddin , Haug Graham C. , Nguyen Viet D. , Porey Arka , Trevino Ramon , Larionov Oleg V. 
Published: August 2022

AbstractStereoselective construction of conjugated dienes and polyenes has remained an enduring synthetic problem owing to the central roles these compounds play in natural product synthesis, methodology, and medicine. This review focuses on recent developments in dienylation as an emerging strategy for the direct installation of unsaturated four-carbon units of conjugated π-systems, outlining the regio- and stereoselectivity, as well as the synthetic scope of reactions with various dienylating reagents and the mechanistic implications of the catalytic cross-coupling processes that are used to enable dienylation.1	Introduction2	Sulfolenes3	1,3-Dienes4	Small-Ring Dienylation Reagents5	Pyrones, Alkynes, and Homoallenylboronates6	Conclusion and Outlook
Optical readout of singlet fission biexcitons in a heteroacene with photoluminescence detected magnetic resonance
Authors: Joshi Gajadhar , Dill Ryan D. , Thorley Karl J. , Anthony John E. , Reid Obadiah G. , Johnson Justin C. 
Published: August 2022

Molecular spin systems based on photoexcited triplet pairs formed via singlet fission (SF) are attractive as carriers of quantum information because of their potentially pure and controllable spin polarization, but developing systems that offer optical routes to readout as well as initialization is challenging. Herein, we characterize the electron spin magnetic resonance change in the photoluminescence intensity for a tailored organic molecular crystal while sweeping a microwave drive up to 10 GHz in a broadband loop structure. We observe resonant transitions for both triplet and quintet spin sublevel populations showing their optical sensitivity and revealing the zero-field parameters for each. We map the evolution of these spectra in both microwave frequency and magnetic field, producing a pattern of optically detected magnetic resonance (ODMR) peaks. Fits to these data using a suitable model suggest significant spin polarization in this system with orientation selectivity. Unusual excitation intensity dependence is also observed, which inverts the sign of the ODMR signal for the triplet features, but not for the quintet. These observations demonstrate optical detection of the spin sublevel population dictated by SF and intermolecular geometry, and highlight anisotropic and multi-scale dynamics of triplet pairs.
Effect of litter system and nest box type on egg production and performance of Ross 308 broiler breeders
Authors: Wegner Marcin , Kokoszynski Dariusz , Biegniewska Milena 
Published: August 2022

Context Type of litter housing system is one of the most important factors affecting egg production and performance of broiler breeders. Aims The study aim was to determine the effect of litter and nest box type on selected production and performance traits of Ross 308 broiler breeders. Methods The study subjects consisted of male and female Ross 308 broiler breeders raised on a commercial poultry farm. In four poultry houses, birds were raised on a slat-litter floor, with a colony nest box type. In four other poultry houses, birds were raised on a litter floor with an open nest box type. Body weight (23 weeks and 57 weeks), feed intake and percent mortality (23–57 weeks), length of laying period, number of eggs, laying percentage and egg weight were determined or calculated and compared between housing systems. Key results Birds reared on a slat-litter floor with colony nest boxes had significantly lower (roosters) or higher (hens) body weight at 23 and 57 weeks of age compared to birds kept on a litter floor with open nest boxes. Both sexes housed on a slat-litter floor were characterised by significantly higher feed intake, significantly lower mortality during the reproductive period (23–57 weeks), and significantly lower egg weight compared to birds raised in the litter floor system. Litter and nest box type had no significant effect on length of laying period, number of eggs, laying percentage, and percent hatchability from set eggs. Conclusions Ross 308 broiler breeders kept on a litter floor with open nest boxes had some better performance parameters, but poorer liveability compared to birds kept on a litter floor and slats with colony nest boxes. The higher body weight of females kept on a slat-litter floor at the end of the reproductive period (57 weeks) compared to the same-age females kept on a litter floor is likely due to higher carcass fatness, which had an adverse effect on the number and weight of hatching eggs. Implications The results of this study may be useful for broiler breeder producers in their decisions about the litter system of these birds.
Bromodomain inhibition overcomes treatment resistance in distinct molecular subtypes of melanoma
Authors: Dar Altaf A. , Bezrookove Vladimir , Nosrati Mehdi , Ice Ryan , Patino John M. , Vaquero Edith M. , Parrett Brian , Leong Stanley P. , Kim Kevin B. , Debs Robert J. , Soroceanu Liliana , Miller James R. , Desprez Pierre-Yves , Cleaver James E. , Salomonis Nathan , McAllister Sean , Kashani-Sabet Mohammed 
Published: August 2022

Therapy of
BRAF
-mutant melanoma with selective inhibitors of BRAF (BRAFi) and MEK (MEKi) represents a major clinical advance but acquired resistance to therapy has emerged as a key obstacle. To date, no clinical approaches successfully resensitize to BRAF/MEK inhibition. Here, we develop a therapeutic strategy for melanoma using bromosporine, a bromodomain inhibitor. Bromosporine (bromo) monotherapy produced significant anti-tumor effects against established melanoma cell lines and patient-derived xenografts (PDXs). Combinatorial therapy involving bromosporine and cobimetinib (bromo/cobi) showed synergistic anti-tumor effects in multiple BRAFi-resistant PDX models. The bromo/cobi combination was superior in vivo to standard BRAFi/MEKi therapy in the treatment-naive
BRAF
-mutant setting and to MEKi alone in the setting of immunotherapy-resistant
NRAS
- and
NF1
-mutant melanoma. RNA sequencing of xenografts treated with bromo/cobi revealed profound down-regulation of genes critical to cell division and mitotic progression. Bromo/cobi treatment resulted in marked DNA damage and cell-cycle arrest, resulting in induction of apoptosis. These studies introduce bromodomain inhibition, alone or combined with agents targeting the mitogen activated protein kinase pathway, as a rational therapeutic approach for melanoma refractory to standard targeted or immunotherapeutic approaches.
Double-port homodyne detection in a squeezed-state interferometry with a binary-outcome data processing
Authors: Zhou Likun , Liu Pan , Jin Guang-Ri 
Published: August 2022

Abstract
Performing homodyne detection at a single output port of a squeezed-state light interferometer and then separating the measurement quadrature into two intervals can realize super-resolving and super-sensitive phase measurements, which is equivalent to a binary-outcome measurement. Obviously, the single-port homodyne detection may lose almost part of the phase information, reducing the estimation precision. Here, we propose a data-processing technique over the double-port homodyne detection, where the two-dimensional measurement quadrature (p
1, p
2) has been divided into two regions. With such a binary-outcome measurement, we estimate the phase shift accumulated in the interferometer by inverting the output signal. By analyzing the full width at half maximum of the signal and the phase sensitivity, we show that both the resolution and the achievable sensitivity are better than that of the previous binary-outcome scheme.
Post-treatment stability after 5 years of retention with vacuum-formed and bonded retainers—a randomized controlled trial
Authors: Krämer Anke , Sjöström Mats , Apelthun Catharina , Hallman Mats , Feldmann Ingalill 
Published: August 2022

SummaryBackgroundRetention after orthodontic treatment is still a challenge and more evidence about post-treatment stability and patients’ perceptions of different retention strategies is needed.ObjectivesThis trial compares removable vacuum-formed retainers (VFR) with bonded cuspid-to-cuspid retainers (CTC) after 5 years of retention.Trial designA single centre two-arm parallel-group randomized controlled trial.MethodsThis trial included 104 adolescent patients, randomized into two groups (computer-generated), using sequentially numbered, opaque, and sealed envelopes. All patients were treated with fixed appliances in both jaws with and without tooth extractions. Patients in the intervention group received a VFR in the mandible (n = 52), and patients in the active comparator group received a CTC (n = 52). Both groups had a VFR in the maxilla. Dental casts at debond (T1), after 6 months (T2), after 18 months (T3), and after 5 years (T4) were digitized and analysed regarding Little’s Irregularity Index (LII), overbite, overjet, arch length, and intercanine and intermolar width. The patients completed questionnaires at T1, T2, T3, and T4.ResultsPost-treatment changes between T1 and T4 in both jaws were overall small. In the maxilla, LII increased significantly (median difference: 0.3 mm), equally in both groups. In the mandible, LII increased significantly in the group VFR/VFR (median difference: 0.6 mm) compared to group VFR/CTC (median difference: 0.1 mm). In both groups, overjet was stable, overbite increased, and arch lengths decreased continuously. Intercanine widths and intermolar width in the mandible remained stable, but intermolar width in the maxilla decreased significantly. No differences were found between groups. Regardless of retention strategy, patients were very satisfied with the treatment outcome and their retention appliances after 5 years.LimitationsIt was not possible to perform blinded assessments of digital models at follow-up.ConclusionsPost-treatment changes in both jaws were small. Anterior alignment in the mandible was more stable with a bonded CTC retainer compared to a removable VFR after 5 years of retention. Patients were equally satisfied with fixed and removable retention appliances.Trial registrationClinicalTrials.gov (NCT03070444).
Epigenome-wide Association Study Analysis of Calorie Restriction in Humans, CALERIETM Trial Analysis
Authors: Ramaker Megan E , Corcoran David L , Apsley Abner T , Kobor Michael S , Kraus Virginia B , Kraus William E , Lin David T S , Orenduff Melissa C , Pieper Carl F , Waziry Reem , Huffman Kim M , Belsky Daniel W 
Published: August 2022

Abstract
Calorie restriction (CR) increases healthy life span and is accompanied by slowing or reversal of aging-associated DNA methylation (DNAm) changes in animal models. In the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIETM) human trial, we evaluated associations of CR and changes in whole-blood DNAm. CALERIETM randomized 220 healthy, nonobese adults in a 2:1 allocation to 2 years of CR or ad libitum (AL) diet. The average CR in the treatment group through 24 months of follow-up was 12%. Whole blood (baseline, 12, and 24 months) DNAm profiles were measured. Epigenome-wide association study (EWAS) analysis tested CR-induced changes from baseline to 12 and 24 months in the n = 197 participants with available DNAm data. CR treatment was not associated with epigenome-wide significant (false discovery rate [FDR] &lt; 0.05) DNAm changes at the individual-CpG-site level. Secondary analysis of sets of CpG sites identified in published EWAS revealed that CR induced DNAm changes opposite to those associated with higher body mass index and cigarette smoking (p &lt; .003 at 12- and 24-month follow-ups). In contrast, CR altered DNAm at chronological-age-associated CpG sites in the direction of older age (p &lt; .003 at 12- and 24-month follow-ups). Although individual CpG site DNAm changes in response to CR were not identified, analyses of sets CpGs identified in prior EWAS revealed CR-induced changes to blood DNAm. Altered CpG sets were enriched for insulin production, glucose tolerance, inflammation, and DNA-binding and DNA-regulation pathways, several of which are known to be modified by CR. DNAm changes may contribute to CR effects on aging.
A bioinformatic-assisted workflow for genome-wide identification of ncRNAs
Authors: Schmal Matthias , Girod Crystal , Yaver Debbie , Mach Robert L , Mach-Aigner Astrid R 
Published: August 2022

Abstract
With the upcoming of affordable Next-Generation Sequencing technologies, the number of known non-protein coding RNAs increased drastically in recent years. Different types of non-coding RNAs (ncRNAs) emerged as key players in the regulation of gene expression on the RNA–RNA, RNA–DNA as well as RNA–protein level, ranging from involvement in chromatin remodeling and transcription regulation to post-transcriptional modifications. Prediction of ncRNAs involves the use of several bioinformatics tools and can be a daunting task for researchers. This led to the development of analysis pipelines such as UClncR and lncpipe. However, these pipelines are limited to datasets from human, mouse, zebrafish or fruit fly and are not able to analyze RNA sequencing data from other organisms. In this study, we developed the analysis pipeline Pinc (Pipeline for prediction of ncRNA) as an enhanced tool to predict ncRNAs based on sequencing data by removing transcripts that show protein-coding potential. Additionally, a feature for differential expression analysis of annotated genes as well as for identification of novel ncRNAs is implemented. Pinc uses Nextflow as a framework and is built with robust and well-established analysis tools. This will allow researchers to utilize sequencing data from every organism in order to reliably identify ncRNAs.