bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-molecule analysis of DNA-binding proteins from nuclear extracts (SMADNE)
Authors: Schaich Matthew A , Schnable Brittani L , Kumar Namrata , Roginskaya Vera , Jakielski Rachel C , Urban Roman , Zhong Zhou , Kad Neil M , Van Houten Bennett 
Published: March 2023

Abstract
Single-molecule characterization of protein–DNA dynamics provides unprecedented mechanistic details about numerous nuclear processes. Here, we describe a new method that rapidly generates single-molecule information with fluorescently tagged proteins isolated from nuclear extracts of human cells. We demonstrated the wide applicability of this novel technique on undamaged DNA and three forms of DNA damage using seven native DNA repair proteins and two structural variants, including: poly(ADP-ribose) polymerase (PARP1), heterodimeric ultraviolet-damaged DNA-binding protein (UV-DDB), and 8-oxoguanine glycosylase 1 (OGG1). We found that PARP1 binding to DNA nicks is altered by tension, and that UV-DDB did not act as an obligate heterodimer of DDB1 and DDB2 on UV-irradiated DNA. UV-DDB bound to UV photoproducts with an average lifetime of 39 seconds (corrected for photobleaching, τc), whereas binding lifetimes to 8-oxoG adducts were &lt; 1 second. Catalytically inactive OGG1 variant K249Q bound oxidative damage 23-fold longer than WT OGG1, at 47 and 2.0 s, respectively. By measuring three fluorescent colors simultaneously, we also characterized the assembly and disassembly kinetics of UV-DDB and OGG1 complexes on DNA. Hence, the SMADNE technique represents a novel, scalable, and universal method to obtain single-molecule mechanistic insights into key protein–DNA interactions in an environment containing physiologically-relevant nuclear proteins.
Hyponatraemia and fluid overload are associated with higher risk of mortality in dialysis patients
Authors: Pinter Jule , Genser Bernd , Moissl Ulrich , Stuard Stefano , Kooman Jeroen , Canaud Bernard , Wanner Christoph 
Published: March 2023

ABSTRACT

Background
The 5-year mortality rate for haemodialysis patients is over 50%. Acute and chronic disturbances in salt and fluid homeostasis contribute to poor survival and are established as individual mortality risk factors. However, their interaction in relation to mortality is unclear.

Methods
We used the European Clinical Database 5 to investigate in a retrospective cohort analysis the relationship between transient hypo- and hypernatremia, fluid status and mortality risk of 72 163 haemodialysis patients from 25 countries. Incident haemodialysis patients with at least one valid measurement of bioimpedance spectroscopy were followed until death or administrative censoring from 1 January 2010 to 4 December 2019. Fluid overload and depletion were defined as &gt;2.5 L above, and −1.1 L below normal fluid status, respectively. N = 2 272 041 recorded plasma sodium and fluid status measurements were available over a monthly time grid and analysed in a Cox regression model for time-to-death.

Results
Mortality risk of hyponatremia (plasma sodium &lt;135 mmol/L) was slightly increased when fluid status was normal [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.18–1.35], increased by half when patients were fluid depleted (HR 1.56, 95% CI 1.27–1.93) and accelerated during fluid overload (HR 1.97, 95% CI 1.82–2.12).

Conclusions
Plasma sodium and fluid status act independently as risk factors on mortality. Patient surveillance of fluid status is especially important in the high-risk subpopulation of patients with hyponatremia. Prospective patient-level studies should examine the effects of chronic hypo- and hypernatremia, risk determinants, and their outcome risk.
The impact of food restriction on liver enzyme levels: a systematic review and meta-analysis
Authors: Huang Hang , Qiu Yunmei , Tang Anyang , Li Wanzhi , Yao Wanyi , Zhong Mei , Yang Ting , Zou Tangbin 
Published: March 2023

Abstract

Context
The relationship between food restriction (FR) and liver enzyme levels, such as alanine transferase (ALT), aspartate transferase (AST), and γ-glutamyl transferase (GGT), has not yet been confirmed.

Objective
A meta-analysis of research articles was conducted to investigate the association of FR and liver enzyme levels.

Data sources
The PubMed, Web of Science, Embase, and Cochrane Library databases were screened for articles published up to April 30, 2022.

Data extraction
Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement methodology was used to search for research articles. Publication bias was detected using Begg’s test. Finally, 17 trials involving 1982 participants and that reported mean value, mean difference, and standard deviation were identified.

Data analysis
Data were described as the weighted mean difference of body mass index, body weight, and standardized mean difference (SMD) of ALT, AST, and GGT. A reduction in ALT level was observed after a FR intervention (total SMD, –0.36, 95% confidence interval [CI], –0.68 to –0.05). GGT levels also were decreased in 4 studies (total SMD, –0.23; 95%CI, –0.33 to –0.14). According to subgroup analysis, serum AST levels decreased in the medium-term (between 5 wk and 6 mo) group (subtotal SMD, –0.48; 95%CI, –0.69 to –0.28).

Conclusion
Existing evidence suggests that dietary restriction improves adult liver enzyme levels. The long-term maintenance of healthy liver enzyme levels, particularly in real-world applications, necessitates additional consideration.
Rice HEAT SHOCK PROTEIN60-3B maintains male fertility under high temperature by starch granule biogenesis
Authors: Lin Sen , Liu Ze , Sun Shiyu , Xue Feiyang , Li Huanjun , Tursun Askar , Cao Lichun , Zhang Long , Wilson Zoe A , Zhang Dabing , Liang Wanqi 
Published: March 2023

AbstractHeat stress has a deleterious effect on male fertility in rice (Oryza sativa), but mechanisms to protect against heat stress in rice male gametophytes are poorly understood. Here, we have isolated and characterized a heat-sensitive male-sterile rice mutant, heat shock protein60-3b (oshsp60-3b), that shows normal fertility at optimal temperatures but decreasing fertility as temperatures increase. High temperatures interfered with pollen starch granule formation and reactive oxygen species (ROS) scavenging in oshsp60-3b anthers, leading to cell death and pollen abortion. In line with the mutant phenotypes, OsHSP60-3B was rapidly upregulated in response to heat shock and its protein products were localized to the plastid. Critically, overexpression of OsHSP60-3B enhanced the heat tolerance of pollen in transgenic plants. We demonstrated that OsHSP60-3B interacted with FLOURY ENDOSPERM6(FLO6) in plastids, a key component involved in the starch granule formation in the rice pollen. Western blot results showed that FLO6 level was substantially decreased in oshsp60-3b anthers at high temperature, indicating that OsHSP60-3B is required to stabilize FLO6 when temperatures exceed optimal conditions. We suggest that in response to high temperature, OsHSP60-3B interacts with FLO6 to regulate starch granule biogenesis in rice pollen and attenuates ROS levels in anthers to ensure normal male gametophyte development in rice.
Implementing a deterministic search algorithm with a single qubit
Authors: Peng Chen-Hui , Bin Liang , He Xin , Sun Yong-Nan , Su Qi-Ping , Yang Chui-Ping 
Published: March 2023

Abstract
Quantum search algorithms have important applications in quantum information, which have been experimentally demonstrated in several quantum systems with database sizes up to 16. We first propose an efficient quantum search scheme based on an optimized Grover’s algorithm and a novel encoding method. With this scheme, a target element can be deterministically searched in a large database using only a single qubit. Then we implement this search scheme in linear optics with database sizes up to 40. Experimental results fit well with the theoretical results, with all fidelities greater than 99.7%. The limitation of the number of elements encoded in a single qubit is also investigated in the experiment. The experimental results indicate that a target state can be successfully searched from a database of size 36 using a single qubit in our laboratory. Since only one qubit and one-qubit gates are required, this search scheme is quite efficient and general, and can be adopted to implement the same task in most quantum systems.
Identification of new candidate drugs for primary Sjögren’s syndrome using a drug repurposing transcriptomic approach
Authors: Felten Renaud , Ye Tao , Schleiss Cedric , Schwikowski Benno , Sibilia Jean , Monneaux Fanny , Dumortier Hélène , Jonsson Roland , Lessard Christopher , Ng Fai , Takeuchi Tsutomu , Mariette Xavier , Gottenberg Jacques-Eric 
Published: March 2023

Abstract

Objectives
To date, no immunomodulatory drug has demonstrated its efficacy in primary SS (pSS). We sought to analyse potential commonalities between pSS transcriptomic signatures and signatures of various drugs or specific knock-in or knock-down genes.

Methods
Gene expression from peripheral blood samples of patients with pSS was compared with that of healthy controls in two cohorts and three public databases. In each of the five datasets, we analysed the 150 most up- and downregulated genes between pSS patients and controls with regard to the differentially expressed genes resulting from the biological action on nine cell lines of 2837 drugs, 2160 knock-in and 3799 knock-down genes in the Connectivity Map database.

Results
We analysed 1008 peripheral blood transcriptomes from five independent studies (868 patients with pSS and 140 healthy controls). Eleven drugs could represent potential candidate drugs, with histone deacetylases and PI3K inhibitors among the most significantly associated. Twelve knock-in genes were associated with a pSS-like profile and 23 knock-down genes were associated with a pSS-revert profile. Most of those genes (28/35, 80%) were interferon-regulated.

Conclusion
This first drug repositioning transcriptomic approach in SS confirms the interest of targeting interferons and identifies histone deacetylases and PI3K inhibitors as potential therapeutic targets.
When it looks like Behçet’s syndrome but is something else: differential diagnosis of Behçet’s syndrome: a two-centre retrospective analysis
Authors: Lötscher Fabian , Kerstens Floor , Krusche Martin , Ruffer Nikolas , Kötter Ina , Turkstra Franktien 
Published: March 2023

Abstract

Objective
To investigate the differential diagnostic spectrum in patients with suspected Behçet’s syndrome (BS) in low prevalence regions. In addition, the number of patients fulfilling the ICBD criteria despite not having BS was evaluated.

Methods
This retrospective analysis was performed in two referral centres for BS. Patients with confirmed BS (clinical diagnosis with fulfilment of ISG criteria or a score of ≥5 points in the ICBD criteria) were excluded. The remaining patients were divided into 11 differential diagnosis categories. If no definitive alternative diagnosis could be established, patients were termed ‘probable BS’ in case of (i) relapsing orogenital aphthosis in the absence of other causes and either HLA-B51 positivity, or origin from an endemic area or presence of an additional typical BS symptom that is not part of the classification criteria, or (ii) with 3–4 points scored in the ICBD criteria.

Results
In total 202 patients were included and categorized as follows: 58 patients (28.7%) as ‘probable BS’, 57 (28.2%) skin disease, 26 (12.9%) chronic pain syndrome, 14 (6.9%) eye disease, 11 (5.4%) spondyloarthropathy, 9 (4.5%) gastrointestinal disease, 7 (3.5%) neurological disease, 4 (2%) arthritis, 3 (1.5%) auto-inflammation, 3 (1.5%) connective tissue disease and 10 (5.0%) miscellaneous disease. HLA-B51 was positive in 55/132 (41.7%); 75/202 (37.1%) of the patients fulfilled the ICBD criteria.

Conclusion
In a low disease prevalence setting, the straightforward application of the ICBD criteria may lead to overdiagnosis of BS. The differential diagnosis of BS is enormously broad. Clinicians should be aware that HLA-B51 positivity is still not considered as a diagnostic feature in BS.
Effect of the new 75-mg orodispersible film of sildenafil on erection and sexual quality of life: insights from an observational study
Authors: Sansone Andrea , Frangione Valeria , Lanzarotti Arturo , Cocci Andrea , Ceruti Carlo , De Sio Marco , Imbimbo Ciro , Mirone Vincenzo , Schips Luigi , Terrone Carlo , Jannini Emmanuele A 
Published: March 2023

AbstractBackgroundThe newly devised orodispersible film (ODF) of sildenafil is the first phosphodiesterase type 5 inhibitor (PDE5i) available in a 75-mg dose. This intermediate dose and the particular properties of the ODF formulation can improve the clinical management of erectile dysfunction (ED) patients.AimWe investigated the effects of the sildenafil ODF 75-mg dose on both sexual quality of life and erectile function based on the results from an observational study in daily practice in Italy.MethodsThis study was a post hoc analysis of results from an observational, real-life study carried out in ED patients at 6 treatment centers in Italy. All subjects were asked to take the prescribed dose of sildenafil ODF at inclusion (visit 1) and to return for a control visit (visit 2) to confirm or adapt the prescribed dose after a minimum of 4 weeks. An end of study control visit (visit 3) was performed after additional 4 weeks.OutcomesErectile function, assessed by the International Index of Erectile Function–Erectile Function (IIEF-EF) domain; sexual quality of life, measured using the sexual quality of life instrument for men (SQoL-M).ResultsAmong the 36 subjects initially recruited for the 75-mg dose, 5 patients dropped out of the study (2 at visit 2 and 3 at visit 3), none of whom due to treatment inefficacy or serious adverse events. At visit 2, the mean (SD) IIEF-EF scores significantly increased (∆ = 7.97 [4.71], P &lt; 0.0001) as SQoL-M scores also did (∆ = 10.76 [10.46], P &lt; 0.0001). At visit 3, IIEF-EF and SQoL-M scores were still significantly improved compared to baseline (∆ = 10.64 [7.01], P &lt; 0.0001, and ∆ = 18.15 [12.32], P &lt; 0.0001, respectively). By ANCOVA, we found no significant effects for age, BMI, previous use of PDE5i, presence of metabolic comorbidities, or smoking habits on study outcomes at both visits 2 and 3.Clinical implicationThe new 75-mg ODF sildenafil formulation is a safe and effective treatment for ED, significantly improving both erectile function and sexual quality of life in patients undergoing treatment.Strengths and limitationsThis is the first study assessing the efficacy of the sildenafil ODF 75-mg dose in a real-life setting. However, the small sample size, possible underlying cultural factors, and limited availability of clinically relevant data may have affected the reliability of our results.ConclusionThe use of the 75 mg ODF formulation for sildenafil represents an effective and safe novel treatment option for ED patients.
Sleep and mental health in recruit paramedics: a 6-month longitudinal study
Authors: Nguyen Elle , Meadley Ben , Harris Rachael , Rajaratnam Shantha M W , Williams Brett , Smith Karen , Bowles Kelly-Ann , Dobbie Megan L , Drummond Sean P A , Wolkow Alexander P 
Published: March 2023

AbstractStudy ObjectivesTo explore potential relationships and longitudinal changes in sleep and mental health in recruit paramedics over the first 6 months of work, and whether sleep disturbances pre-emergency work predict future mental health outcomes.MethodsParticipants (N = 101, 52% female, Mage = 26 years) completed questionnaires prior to (baseline), and after 6 months of emergency work to assess for symptoms of insomnia, obstructive sleep apnea, post-traumatic stress disorder (PTSD), depression, anxiety, and trauma exposure. At each timepoint, participants also completed a sleep diary and wore an actigraph for 14 days to assess sleep patterns. Correlations between baseline sleep and mental health were conducted and changes in these variables across timepoints were examined using linear mixed models. Hierarchical regressions assessed whether sleep at baseline predicted mental health at follow-up.ResultsInsomnia and depression symptoms, and total sleep time increased while sleep onset latency decreased across the first 6 months of emergency work. Participants experienced an average of 1 potentially traumatic event during the 6-month period. Baseline insomnia predicted increased depression symptoms at the 6-month follow-up, while baseline wake after sleep onset predicted follow-up PTSD symptoms.ConclusionResults highlight an increase in insomnia and depression across the initial months of emergency work, while sleep disturbances before emergency work were identified as potential risk factors for the development of depression and PTSD among paramedics in their early career. Screening and early interventions targeting poor sleep at the beginning of emergency employment may assist in reducing the risk of future mental health outcomes in this high-risk occupation.
Manipulation of Signal Gradient and Transcription Factors Recapitulates: Multiple Hypothalamic Identities
Authors: Yamamoto Maho , Ong Agnes Lee Chen , Shinozuka Takuma , Shirai Manabu , Sasai Noriaki 
Published: March 2023

Abstract
During development, the hypothalamus emerges from the ventral diencephalon and is regionalized into several distinct functional domains. Each domain is characterized by a different combination of transcription factors, including Nkx2.1, Nkx2.2, Pax6, and Rx, which are expressed in the presumptive hypothalamus and its surrounding regions, and play critical roles in defining each area.
Here, we recapitulated the molecular networks formed by the gradient of Sonic Hedgehog (Shh) and the aforementioned transcription factors. Using combinatorial experimental systems of directed neural differentiation of mouse embryonic stem (ES) cells, as well as a reporter mouse line and gene overexpression in chick embryos, we deciphered the regulation of transcription factors by different Shh signal intensities. We then used CRISPR/Cas9 mutagenesis to demonstrate the mutual repression between Nkx2.1 and Nkx2.2 in a cell-autonomous manner; however, they induce each other in a non-cell-autonomous manner. Moreover, Rx resides upstream of all these transcription factors and determines the location of the hypothalamic region. Our findings suggest that Shh signaling and its downstream transcription network are required for hypothalamic regionalization and establishment.
Utility of Inter-Frequency Amplitude Ratio of Vestibular-Evoked Myogenic Potentials in Identifying Meniere’s Disease: A Systematic Review and Meta-Analysis
Authors: Singh Niraj Kumar , Kumar Prawin , Jagadish Nirmala , Mendhakar Akshay , Mahajan Yatin 
Published: March 2023

Objectives:
A recently devised parameter of vestibular-evoked myogenic potential (VEMP) based on the principles of frequency tuning is the inter-frequency amplitude ratio (IFAR). It refers to the ratio of the amplitude of 1000 Hz tone burst evoked VEMP to 500 Hz evoked tone burst. A pathology like Meniere’s disease changes the frequency response and alters the frequency tuning of the otolith organs. Because IFAR is based on the principle of frequency tuning of VEMP, it is likely to help identify Meniere’s disease. Few studies in the last decade have investigated the utility of IFAR in identifying Meniere’s disease. However, a systematic review and a meta-analysis on IFAR in Meniere’s disease are lacking. The present study investigates whether the IFAR of VEMP helps identify Meniere’s disease and differentiates it from healthy ears and other vestibular pathologies.

Design:
The present study is a systematic review and a meta-analysis. The studies investigating the IFAR of cervical and ocular VEMPs in Meniere’s disease, healthy controls, and other vestibular pathologies were searched across research databases such as PubMed, Science Direct, and Scopus. The search strategy was developed using the PICO (population, intervention, comparison, and outcomes) format, and Medical Subject Headings (MeSH) terms and Boolean operators were employed. The systematic review was performed using the Rayyan software, whereas the Review Manager software was used to carry out the meta-analysis. A total of 16,605 articles were retrieved from the databases. After the duplicate removal, 2472 articles remained. These were eliminated using title screening, abstract screening, and full-length inspections. A total of nine articles were found eligible for quality assessment and meta-analysis, and the New Castle-Ottawa Scale was used for quality assessment. After the data extraction, 24 six articles were found to have the desired data format for the meta-analysis.

Results:
The results showed significantly higher IFAR in the affected ears of individuals in the Meniere’s disease group than in the control group’s unaffected ears. There was no significant difference between the unaffected ears of individuals in the Meniere’s disease group and the ears of the control group. The only study on Meniere’s disease and benign paroxysmal positional vertigo found significantly larger ocular VEMP IFAR in ears with Meniere’s disease than in benign paroxysmal positional vertigo.

Conclusions:
This systematic review and meta-analysis found IFAR efficient in differentiating Meniere’s disease from healthy controls. We also found an enhanced IFAR as a potential marker for Meniere’s disease. However, more investigations are needed to confirm the utility of an enhanced IFAR value in the exclusive identification of Meniere’s disease.
Effect of Implant Linkage on Axial and Rotational Stiffness of Nail–Plate Constructs for Comminuted Distal Femoral Fractures
Authors: Lin Charles C. , Parody Nicholas , Anil Utkarsh , Egol Kenneth A. 
Published: March 2023

Objectives:
To determine the effect of linking the intramedullary nail and the laterally applied locking plate to treat comminuted distal femur fractures and allow for immediate weight bearing.

Methods:
Comminuted extra-articular distal femur fractures were created in 16 synthetic osteoporotic femurs and split into 2 groups: linked versus unlinked. In the linked construct, in addition to standard plate fixation and proximal locking of the nail, 2 nonthreaded locking bolts (prototypes) were placed through both the plate and the nail. In the unlinked construct, the same number of screws affixed the plate to the bone but were directed around the nail, and separate distal interlocking screws were placed for nail fixation. Each specimen underwent sequential axial and torsional loading, and axial and torsional stiffness were calculated and compared.

Results:
On average, the unlinked constructs demonstrated a greater axial stiffness at all levels of axial loading, and linked constructs demonstrated greater average rotational stiffness. However, there were no statistically significant differences (P > 0.189) between the linked and unlinked groups at any axial or torsional load.

Conclusion:
In distal femur fractures with metaphyseal comminution, there were no significant differences in axial or torsional stiffness when linking the plate to the nail. Linking the construct seems to provide no significant mechanical advantage compared with the unlinked environment, but it may be a useful strategy to reduce nail “traffic” in the distal segment with no significant disadvantage.