bluuebunny/crossref_metadata_2025 huggingface dataset:
XMM-Newton-discovered Fast X-ray Transients: host galaxies and limits on contemporaneous detections of optical counterparts
Authors: Eappachen D , Jonker P G , Quirola-Vásquez J , Sánchez D Mata , Inkenhaag A , Levan A J , Fraser M , Torres M A P , Bauer F E , Chrimes A A , Stern D , Graham M J , Smartt S J , Smith K W , Ravasio M E , Zabludoff A I , Yue M , Stoppa F , Malesani D B , Stone N C , Wen S
Published: December 2023

Extragalactic fast X-ray transients (FXTs) are a class of soft (0.3–10 keV) X-ray transients lasting a few hundred seconds to several hours. Several progenitor mechanisms have been suggested to produce FXTs, including supernova shock breakouts, binary neutron star mergers, or tidal disruptions involving an intermediate-mass black hole and a white dwarf. We present detailed host studies, including spectroscopic observations of the host galaxies of seven XMM-Newton-discovered FXTs. The candidate hosts lie at redshifts 0.0928 <z < 0.645 implying peak X-ray luminosities of 1043 erg s−1<LX < 1045 erg s−1 and physical offsets of 1 kpc < rproj < 22 kpc. These observations increase the number of FXTs with a spectroscopic redshift measurement by a factor of 2, although we note that one event is re-identified as a Galactic flare star. We infer host star formation rates and stellar masses by fitting the combined spectroscopic and archival photometric data. We also report on a contemporaneous optical counterpart search to the FXTs in Pan-STARRS and ATLAS by performing forced photometry at the position of the FXTs. We do not find any counterpart in our search. Given our constraints, including peak X-ray luminosities, optical limits, and host properties, we find that XRT 110 621 is consistent with an supernova shock breakout (SN SBO) event. Spectroscopic redshifts of likely host galaxies for four events imply peak X-ray luminosities that are too high to be consistent with SN SBOs, but we are unable to discard either the binary neutron star or white dwarf–intermediate-mass black hole tidal disruption event scenarios for these FXTs.
Atomic diffusion and mixing in old stars – VIII. Chemical abundance variations in the globular cluster M4 (NGC 6121)
Authors: Nordlander T , Gruyters P , Richard O , Korn A J
Published: December 2023

Variations in chemical abundances with evolutionary phase have been identified among stars in globular and open clusters with a wide range of metallicities. In the metal-poor clusters, these variations compare well with predictions from stellar structure and evolution models considering the internal diffusive motions of atoms and ions, collectively known as atomic diffusion, when moderated by an additional mixing process with a fine-tuned efficiency. We present here an investigation of these effects in the Galactic globular cluster NGC 6121 (M4) ([Fe/H] = −1.13) through a detailed chemical abundance analysis of 86 stars using high-resolution ESO Very Large Telescope (VLT) Fibre Large Array Multi Element Spectrograph (FLAMES) spectroscopy. The stars range from the main-sequence turnoff point (TOP) to the red giant branch (RGB) just above the bump. We identify C-N-O and Mg-Al-Si abundance anticorrelations, and confirm the presence of a bimodal population differing by 1 dex in nitrogen abundance. The composition of the second-generation stars imply pollution from both massive (20–40 $\rm M_{\odot }$) and asymptotic giant branch stars. We find evolutionary variations in chemical abundances between the TOP and RGB, which are robust to uncertainties in stellar parameters and modelling assumptions. The variations are weak, but match predictions well when employing efficient additional mixing. Without correcting for Galactic production of lithium, we derive an initial lithium abundance 2.63 ± 0.10, which is marginally lower than the predicted primordial big-bang nucleosynthesis value.
Ascertainment Bias in the Genomic Test of Positive Selection on Regulatory Sequences
Authors: Jiang Daohan , Zhang Jianzhi
Published: December 2023

Evolution of gene expression mediated by cis-regulatory changes is thought to be an important contributor to organismal adaptation, but identifying adaptive cis-regulatory changes is challenging due to the difficulty in knowing the expectation under no positive selection. A new approach for detecting positive selection on transcription factor binding sites (TFBSs) was recently developed, thanks to the application of machine learning in predicting transcription factor (TF) binding affinities of DNA sequences. Given a TFBS sequence from a focal species and the corresponding inferred ancestral sequence that differs from the former at n sites, one can predict the TF-binding affinities of many n-step mutational neighbors of the ancestral sequence and obtain a null distribution of the derived binding affinity, which allows testing whether the binding affinity of the real derived sequence deviates significantly from the null distribution. Applying this test genomically to all experimentally identified binding sites of 3 TFs in humans, a recent study reported positive selection for elevated binding affinities of TFBSs. Here, we show that this genomic test suffers from an ascertainment bias because, even in the absence of positive selection for strengthened binding, the binding affinities of known human TFBSs are more likely to have increased than decreased in evolution. We demonstrate by computer simulation that this bias inflates the false positive rate of the selection test. We propose several methods to mitigate the ascertainment bias and show that almost all previously reported positive selection signals disappear when these methods are applied.
Abrogation of the G2/M checkpoint as a chemosensitization approach for alkylating agents
Authors: Lang Fengchao , Cornwell James A , Kaur Karambir , Elmogazy Omar , Zhang Wei , Zhang Meili , Song Hua , Sun Zhonghe , Wu Xiaolin , Aladjem Mirit I , Aregger Michael , Cappell Steven D , Yang Chunzhang
Published: December 2023

Background

The cell cycle is tightly regulated by checkpoints, which play a vital role in controlling its progression and timing. Cancer cells exploit the G2/M checkpoint, which serves as a resistance mechanism against genotoxic anticancer treatments, allowing for DNA repair prior to cell division. Manipulating cell cycle timing has emerged as a potential strategy to augment the effectiveness of DNA damage-based therapies.

Methods

In this study, we conducted a forward genome-wide CRISPR/Cas9 screening with repeated exposure to the alkylating agent temozolomide (TMZ) to investigate the mechanisms underlying tumor cell survival under genotoxic stress.

Results

Our findings revealed that canonical DNA repair pathways, including the Ataxia–telangiectasia mutated (ATM)/Fanconi and mismatch repair, determine cell fate under genotoxic stress. Notably, we identified the critical role of PKMYT1, in ensuring cell survival. Depletion of PKMYT1 led to overwhelming TMZ-induced cytotoxicity in cancer cells. Isobologram analysis demonstrated potent drug synergy between alkylating agents and a Myt1 kinase inhibitor, RP-6306. Mechanistically, inhibiting Myt1 forced G2/M-arrested cells into an unscheduled transition to the mitotic phase without complete resolution of DNA damage. This forced entry into mitosis, along with persistent DNA damage, resulted in severe mitotic abnormalities. Ultimately, these aberrations led to mitotic exit with substantial apoptosis. Preclinical animal studies demonstrated that the combination regimen involving TMZ and RP-6306 prolonged the overall survival of glioma-bearing mice.

Conclusions

Collectively, our findings highlight the potential of targeting cell cycle timing through Myt1 inhibition as an effective strategy to enhance the efficacy of current standard cancer therapies, potentially leading to improved disease outcomes.
Breaking Barriers: A Single-Center Real-World Experience With Recruitment and Administration of COVID-19 Monoclonal Antibodies and Opportunities for Improvement
Authors: Brenner Sara , Knee Alexander , Salvador Douglas , Housman Erica , Fernandez Gladys , Paez Armando
Published: December 2023

We conducted a retrospective exploratory study evaluating factors associated with selection to receive and infusion with coronavirus disease 2019 monoclonal antibodies. While priority was given to high-risk patients, patients with increased Social Vulnerability Index scores were less likely to present for infusion, raising concern that social factors created barriers to treatment.
Evaluating the Impact of Source-specific Order Sets for Sepsis on Empiric Antibiotic Selection in the Emergency Department
Authors: Menendez Alvarado Lourdes R , Margulis Landayan Alice , Morell Jason , Wasielewski Anthony S , Zhang Zhenwei , Levine Richard , Gauthier Timothy P
Published: December 2023

This retrospective cohort study found that implementing source-specific antibiotic order sets for sepsis in the emergency department increased appropriate empiric antibiotic selection from 51% to 74% (P = .01).
Targeted A-to-G base editing in the organellar genomes of Arabidopsis with monomeric programmable deaminases
Authors: Zhou Chang , Okuno Miki , Nakazato Issei , Tsutsumi Nobuhiro , Arimura Shin-ichi
Published: December 2023

Plastids and mitochondria are 2 intracellular organelles containing DNA-encoding partial but essential components for their roles, photosynthesis, and respiration. Precise base editing in both plastid and mitochondrial genomes would benefit their gene functional analysis and crop breeding. Targeted base editing in organellar genomes relies on a protein-based genome-editing system that uses the TALE-DNA recognition motif with deaminases. This is because the efficient delivery of guide RNA for clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 systems into organelles is currently impossible. Since TALE-based base editors used in organellar genomes are usually dimeric types, in this study, we used targeted A-to-G base editing in Arabidopsis (Arabidopsis thaliana) plastid and mitochondrial genomes with monomeric TALE-based deaminase for easier assembling of vectors. As a result, inheritable targeted A-to-G base editing of adenosine triphosphatase subunit 6-2 (atp6-2) in plant mitochondrial genomes and of 16S ribosomal RNA (16S rRNA) in plastid genomes of Arabidopsis was successfully induced by monomeric TALE-based adenine deaminase (AD) without off-target mutations. The monomeric TALE-based adenine deaminases also demonstrated a preference for editing the 8th T on the same strand from the recognition end. Phenotypic analysis showed that A-to-G conversion at 1139A of plastid 16S rRNA conferred substantial spectinomycin resistance in Arabidopsis, but not the other 2 potential-resistant mutations at 1131T and 1137T, predicted from the previous bacterial data. Our study demonstrated the feasibility of monomeric TALE-based ADs in plant organelles and their potential contribution to the functional analyses of plant organelles with easier assembling.
Localized measurements of water potential reveal large loss of conductance in living tissues of maize leaves
Authors: Jain Piyush , Huber Annika E , Rockwell Fulton E , Sen Sabyasachi , Holbrook Noel Michele , Stroock Abraham D
Published: December 2023

The water status of the living tissue in leaves between the xylem and stomata (outside xylem zone (OXZ) plays a critical role in plant function and global mass and energy balance but has remained largely inaccessible. We resolve the local water relations of OXZ tissue using a nanogel reporter of water potential (ψ), AquaDust, that enables an in situ, nondestructive measurement of both ψ of xylem and highly localized ψ at the terminus of transpiration in the OXZ. Working in maize (Zea mays L.), these localized measurements reveal gradients in the OXZ that are several folds larger than those based on conventional methods and values of ψ in the mesophyll apoplast well below the macroscopic turgor loss potential. We find a strong loss of hydraulic conductance in both the bundle sheath and the mesophyll with decreasing xylem potential but not with evaporative demand. Our measurements suggest the OXZ plays an active role in regulating the transpiration path, and our methods provide the means to study this phenomenon.
Therapeutic Effects of Hematopoietic Stem Cell Derived From Gene-Edited Mice on β654-Thalassemia
Authors: Lu Dan , Gong Xiuli , Guo Xinbing , Chen Yanwen , Zhu Yiwen , Fang Yudan , Cai Qin , Xu Miao , Yang Hua , Li Dali , Zeng Yitao , Zeng Fanyi
Published: December 2023

β-thalassemia is an inherited blood disease caused by reduced or inadequate β-globin synthesis due to β-globin gene mutation. Our previous study developed a gene-edited mice model (β654-ER mice) by CRISPR/Cas9-mediated genome editing, targeting both the βIVS2-654 (C > T) mutation site and the 3ʹ splicing acceptor site at 579 and corrected abnormal β-globin mRNA splicing in the β654-thalassemia mice. Herein, we further explored the therapeutic effect of the hematopoietic stem cells (HSCs) from β654-ER mice on β-thalassemia by consecutive HSC transplantation. The results indicated that HSC transplantation derived from gene-edited mice can significantly improve the survival rate of mice after lethal radiation doses and effectively achieve hematopoietic reconstruction and long-term hematopoiesis. Clinical symptoms, including hematologic parameters and tissue pathology of transplanted recipients, were significantly improved compared to the non-transplanted β654 mice. The therapeutic effect of gene-edited HSC transplantation demonstrated no significant difference in hematological parameters and tissue pathology compared with wild-type mouse-derived HSCs. Our data revealed that HSC transplantation from gene-edited mice completely recovered the β-thalassemia phenotype. Our study systematically investigated the therapeutic effect of HSCs derived from β654-ER mice on β-thalassemia and further confirmed the efficacy of our gene-editing approach. Altogether, it provided a reference and primary experimental data for the clinical usage of such gene-edited HSCs in the future.
Ten years of using key characteristics of human carcinogens to organize and evaluate mechanistic evidence in IARC Monographs on the identification of carcinogenic hazards to humans: Patterns and associations
Authors: Rusyn Ivan , Wright Fred A
Published: December 2023

Systematic review and evaluation of mechanistic evidence using the Key Characteristics approach was proposed by the International Agency for Research on Cancer (IARC) in 2012 and used by the IARC Monographs Working Groups since 2015. Key Characteristics are 10 features of agents known to cause cancer in humans. From 2015 to 2022, a total of 19 Monographs (73 agents combined) used Key Characteristics for cancer hazard classification. We hypothesized that a retrospective analysis of applications of the Key Characteristics approach to cancer hazard classification using heterogenous mechanistic data on diverse agents would be informative for systematic reviews in decision-making. We extracted information on the conclusions, data types, and the role mechanistic data played in the cancer hazard classification from each Monograph. Statistical analyses identified patterns in the use of Key Characteristics, as well as trends and correlations among Key Characteristics, data types, and ultimate decisions. Despite gaps in data for many agents and Key Characteristics, several significant results emerged. Mechanistic data from in vivo animal, in vitro animal, and in vitro human studies were most impactful in concluding that an agent could cause cancer via a Key Characteristic. To exclude the involvement of a Key Characteristic, data from large-scale systematic in vitro testing programs such as ToxCast, were most informative. Overall, increased availability of systemized data streams, such as human in vitro data, would provide the basis for more confident and informed conclusions about both positive and negative associations and inform expert judgments on cancer hazard.
Parking choice behaviour analysis of rural residents based on the latent variable random forest model
Authors: Zhu Minqing , Zhao Bo , Cui Hongjun , Yao Sheng , Xu Feng
Published: December 2023

The imbalance of rural parking supply and demand has a great impact on traffic congestion and environmental pollution, which has attracted the attention of many scholars as well as policymakers. However, most of the current research on parking choice focuses on urban business and residential areas rather than on rural parking choice behaviour, and focuses on the analysis of observable factors, ignoring the internal relationship with potential variables. This study considers the heterogeneity of individuals and uses the random forest (RF) algorithm to construct a model of rural residents’ willingness to choose parking with both latent and explicit variables, to explore how much and in what ways individual characteristics and parking characteristics affect rural residents’ parking choices, and to explore parking planning programmes and strategies that are truly applicable to rural areas. The results of the study suggest that the safety and convenience of the parking environment are key factors influencing the parking choice behaviour of rural residents, and can greatly improve the predictive accuracy of the parking willingness model. Upon comparison, it is found that the application of the RF algorithm is also significantly better than the logit model in terms of prediction effect, indicating that there is a nonlinear effect among the factors influencing the parking choice behaviour of rural residents and that the RF model with the addition of latent variables provides a better explanatory ability for the study of the parking choice behaviour of rural residents.
Health disparities in gout
Authors: Helget Lindsay N. , Mikuls Ted R.
Published: December 2023

Purpose of review

Gout, the most common type of inflammatory arthritis in the world, is characterized by painful episodes of arthritis linked by asymptomatic intercritical periods of hyperuricemia. Once characterized as a disease of wealthy white men, contemporary evidence demonstrates gout disproportionately afflicts racial/ethnic minorities, Indigenous populations and other underrepresented groups leading to significant health disparities.

Recent findings

Herein, we review the current literature reporting a higher incidence and prevalence of gout in racial/ethnic minorities and Indigenous populations, in addition to a growing gout burden reported in females. We also examine how these population are more likely to receive suboptimal treatment for flares and chronic phases of gout. Additionally, we examine biologic and social health determinants that may be contributing to these findings.

Racial/ethnic minorities, Indigenous populations, and females have experienced a disproportionate rise in the prevalence and incidence of gout in recent years, are more likely to seek acute medical care and are less likely to receive optimal long-term care for gout with urate lowering therapy. Mechanisms underpinning these findings appear to be multifactorial and include differences in social determinants of care and in some cases may be due to population differences in select biologic factors such as differences in age, sex, genetics.
Social Support, eHealth Literacy, and mHealth Use in Older Adults With Diabetes
Authors: Kim Minjin , Kim Beomsoo , Park Sunhee
Published: December 2023

Mobile healthcare has emerged as a prominent technological solution for self-management of health. However, the development and utilization of tailored mobile healthcare applications for older adults with diabetes mellitus remain limited. This study examined the relationship between social support and mobile healthcare use and further explored how this relationship varies with eHealth literacy and application design among older adults with diabetes mellitus. A descriptive cross-sectional trial was conducted with a structured self-report questionnaire, surveying 252 South Korean older adults with diabetes mellitus via offline and online modes. The mediating effect and moderated mediating effect were analyzed with the PROCESS macro of SPSS. eHealth literacy mediated the relationship between social support and mobile healthcare use. High levels of eHealth literacy and social support may increase mobile healthcare use among older adults with diabetes. Application design aesthetics facilitated mobile healthcare use. Future researchers, healthcare providers, and developers can contribute to the development of tailored mobile healthcare applications for older adults with diabetes mellitus by considering application design aspects such as font size, color, and menu configuration.
Virtual Reality–Based Education Program for Managing Behavioral and Psychological Symptoms of Dementia
Authors: Cheon Hongjin , Song Jun-Ah , Kim Jiyeon , Jung Sua , Kim Gerard Jounghyun
Published: December 2023

This study aims to develop a virtual reality–based education program for managing behavioral and psychological symptoms of dementia for family carers of persons living with dementia and investigate the feasibility for users. The program was developed through literature review, interviews with family carers, surveys, and expert content validity assessment. User feasibility was evaluated quantitatively through a questionnaire on usefulness, ease of use, and satisfaction, and qualitatively through participant interviews. The program was produced in two parts, Type 1 and Type 2, consisting of three and six episodes, respectively. Participants showed a high level of satisfaction with overall program scores of 4.28 ± 0.66 and 4.34 ± 0.41 for the two evaluations. Participants also expressed that both programs were helpful, Type 1 for achieving changes in attitude associated with more understanding of persons living with dementia and Type 2 for acquiring coping methods through communication training. Use of the virtual reality device was not inconvenient and was identified as helpful due to the high immersion experience. Results of this study confirmed that family carers had no resistance to education using new technologies such as virtual reality devices and that virtual reality–based education could be effective for training family carers.
Selective Laser Trabeculoplasty as a Substitute for Medications in Patients with Mild-to-moderate Glaucoma in the Brazilian Public Health System
Authors: Barbosa Leopoldo Ernesto Oiticica , Barboza Wilma Lelis , Guedes Ricardo Paletta , Pereira Clarissa dos Reis , Susanna Remo , Hatanaka Marcelo
Published: December 2023

Précis:

Selective laser trabeculoplasty can be used as a substitute for medications in patients with mild-to-moderate glaucoma, reducing the cost of eye drop distribution in the Brazilian public health system.

Purpose:

To observe the effectiveness of selective laser trabeculoplasty (SLT) as a substitute for eye drops in patients with open angle glaucoma in the Brazilian Public Health System.

Materials and Methods:

SLT was performed bilaterally after medication washout. This is a prospective interventional study comparing intraocular pressure (IOP) when using eye drops at baseline (post-washout), and at 12-month follow-up after SLT. Medication was added if the target IOP was not achieved, following the Brazilian Public Health System eye drops protocol, based on medication costs. Absolute (without eye drops) and qualified (with eye drops) success were measured with IOP ≤ 21, IOP ≤ 18, IOP ≤ 15 and IOP ≤ 12 mm Hg. Besides IOP evolution, the ability to reduce IOP (in %), and eye drops reduction were evaluated.

Results:

Ninety-two eyes of 46 patients were included, 70 eyes with mild glaucoma and 22 with moderate glaucoma; the mean number of eye drops was 2.26±1.06 (82.6% were using a prostaglandin analogue), and post-washout IOP of 21.10±5.24 mm Hg. There was relative success at IOP ≤18 mm Hg, where the mild group had greater success than the moderate group (88.1% vs. 71.4%, P=0.824). The average IOP reductions were 23.04% and 25.74% at 6 and 12 months, respectively. The average number of eye drops was 1.02, with 1.1% using a prostaglandin analogue. Furthermore, 68.19% of the patients had a decrease in the quantity of eye drops used.

Conclusion:

SLT is effective in reducing IOP and replacing eye drops in patients in the Brazilian Public Health System. Moreover, there was a significant reduction in the use of prostaglandin analogues.
Predictors of Glaucoma After Pediatric Cataract Surgery
Authors: Vilares-Morgado Rodrigo , Ferreira Margarida , Godinho Gonçalo , Melo António Benevides , Barbosa-Breda João , Magalhães Augusto , Estrela-Silva Sérgio
Published: December 2023

Précis:

Glaucoma after pediatric cataract surgery is common and challenging. Age at surgery and the presence of microcornea or other anterior segment (AS) abnormalities can be used to identify those at greatest risk.

Objective:

To establish risk factors for developing glaucoma after pediatric cataract surgery [glaucoma following cataract surgery (GFCS)].

Methods:

Single-center, retrospective, longitudinal study of patients who underwent lensectomy for pediatric cataracts from 2008 to 2020. Included eyes presented with congenital or acquired pediatric cataracts or an anterior form of persistent fetal vasculature, and a follow-up of at least 1 year. Exclusion criteria were the presence of preexisting intraocular pressure elevation, congenital glaucoma, syndromic cataracts, and a history of trauma or uveitis. Demographic and clinical data were collected. Our primary outcome was the development of GFCS. Multivariable logistic regression with generalized estimating equations was used to model the association between potential predictors and the risk of GFCS.

Results:

A total of 110 eyes from 74 patients were included, 38 with unilateral and 36 with bilateral pediatric cataract surgery. The average surgery age was 24.71 ± 37.26 months, with 74 eyes (67.3%) undergoing surgery ≤12 weeks of age. Patients were followed for 9.96 ± 3.64 years after surgery. Twenty-eight eyes (25.45%) developed GFCS, all requiring glaucoma surgery. In multivariable analysis, surgery before 12 weeks of age [odds ratio (OR): 34.74; P < 0.001], presence of microcornea (OR: 12.90; P = 0.002), and presence of other AS abnormalities (OR: 52.71; P < 0.001) were significantly associated with the development of GFCS.

Conclusions:

The development of GFCS is a common and relevant adverse event after pediatric cataract surgery whose management is challenging. Age at surgery, the presence of microcornea, and the presence of other AS abnormalities can be used to identify those at greatest risk.
Improving Glaucoma Patients’ Quality of Life and Adherence With a Digital Health Application: [RETRACTED]
Authors: Blanke Lena , Zinsmeister Leonie , Schnell Stephan , Steinhorst Kira , Lämmer Robert , Michelson Georg
Published: December 2023

Précies:

Empowering glaucoma patients to access their individual glaucoma related health data by using a digital health application leads to a significant improvement in quality of life and adherence.

Purpose:

Evaluate the effectiveness of improvement of glaucoma associated quality of life and adherence in patients using a digital health application.

Patients and Methods:

A prospective randomized monocentric controlled study of 77 patients with primary open angle glaucoma. Patients were recruited at the University Hospital Erlangen. Patients in the intervention group tracked their intraocular pressure, symptoms and therapy using a digital application. Based on the collected data the SmartTonoTracker® gave patients simple statistics and basic recommendations for further treatment. An increasing score on the GlauQol-36 item questionnaire and the MMAS-8 score, conducted at baseline and follow-up by the intervention group, was considered successful. Statistical analysis was conducted using the unpaired t-test, paired t-test, Man-Whitney-U test, frequency analysis, frequency distribution and Pearson-correlation.

Results:

Significant difference in the patients´ glaucoma-associated quality of life between the intervention group (rate of improvement: 7.6%, P=0.047), and the control group (rate of improvement: 0.17%, P=0.047) was shown. Also, a significant difference in adherence between the intervention group, showing a 9.8% rate of improvement (P=0.002), and the control group, showing a 3.8% rate of improvement (P=0.002), was shown.

Conclusion:

Enabling patients to access individual health related glaucoma data by using a digital health application and supporting them with information on their disease led to an improvement in glaucoma-associated quality of life and adherence.
Rosa26 Locus Is Inactive in Spermatogenesis of C57BL/6 Mice
Authors: Wang Honglian , Peng Ze , Li Yuqing , Lai Junyu , Wang Li
Published: December 2023

Background:

The mouse Rosa26 locus demonstrates ubiquitous transcriptional activity, encoding long noncoding RNAs (LncRNAs) with no functional significance in various types of tissues and cells. It is widely employed in targeting transgene knock-in studies. However, the expression pattern of Rosa26 in the testes remains elusive. In this study, we conducted a detailed transcriptional analysis of the Rosa26 locus during mouse spermatogenesis.

Methods:

The transcriptional activity of the Rosa26 locus in the testes was assessed through immunohistochemistry or direct fluorescence observation in two Rosa26 locus-targeting knock-in mouse lines, Rosa26-Flag-Cas9 and Rosa26-mT/mG, both with a C57BL/6 background. The two mouse lines feature constitutively expressed Flag-tagged Cas9 and red fluorescent membrane-tethered tdTomato (mTomato) proteins.

Results:

In Rosa26-Flag-Cas9 mice, immunostaining of testis sections revealed robust expression of the Flag-Cas9 transgene in spermatogonia adjacent to the basement membrane of seminiferous tubules. However, its expression was absent in germ cells undergoing spermatogenesis in seminiferous tubules and in maturing spermatids in the epididymis. The transgene was also observed in intertubular Leydig cells and epididymal epithelia but was absent in Sertoli cells. Similarly, in Rosa26-mT/mG mice, fluorescence microscopy showed a complete absence of mTomato expression in the spermatogonial lineage and Sertoli cells. However, robust mTomato expression was observed in intertubular Leydig cells out of the seminiferous tubules and epididymal epithelia.

Conclusion:

Our findings suggest that the Rosa26 locus is inactive during spermatogenesis, indicating that functional gene studies by targeting knock-in transgenes at the Rosa26 locus in the spermatogonial lineage may not be applicable in C57BL/6 mice.
Perspective on the Modern Interpretation of the Property Theory of Mild-natured and Sweet-flavored Traditional Chinese Medicine via Gut Microbiota Modulation
Authors: Li Leilei , Yang Ya'nan , Cao Ying , Zhan Jiaguo , Wu Yan , Wu Chongming
Published: December 2023

The property theory of traditional Chinese medicine (TCM) has guided its clinical application for thousands of years. Although the TCM modernization project has made significant progress, several challenges, such as identifying modern biological indicators, remain. Recent investigations have demonstrated that the gut microbiota contributes to the metabolism and efficacy of TCMs, providing a potential indicator of TCM properties. To investigate whether the gut microbiota can partially interpret the property theory of TCM, we searched the “PubMed” and “China National Knowledge Infrastructure” databases using “gut microbiota” and “traditional Chinese medicine” as keywords. This review mainly focused on the relationship between mild-natured and sweet-flavored TCMs (MS-TCMs) and the gut microbiota. We discovered that MS-TCMs can recalibrate the gut microbiota to alleviate various diseases. At the family level, MS-TCMs upregulated Erysipelotrichaceae, Verrucomicrobiaceae, Bacteroidaceae, Christensenellaceae, Lactobacillaceae, and Prevotellaceae, while downregulating Enterobacteriaceae, Rikenellaceae4, and S24-7. At the genus level, MS-TCMs increased the abundance of Ruminococcus, Turicibacter, Parabacteroides, Dubosiella, Bifidobacterium, Bacteroides, Lactobacillus, Oscillospira, and Prevotella, and decreased the abundance of Parasutterella, Mucispirillum, Lachnoclostridium, Escherichia, Enterococcus, Butyricicoccus, Clostridiales, Blautia, Desulfovibrio, and Oscillibacter. Mechanistically, changes in gut bacteria can influence the levels of metabolites such as short-chain fatty acids, lipopolyaccharides, and neurotransmitters, which further regulate a series of physiological signaling pathways within the host. Overall, analyzing the TCM–microbiota interaction is an effective means to reveal the mechanisms of TCM, suggesting that the gut microbiota can be developed into a modern indicator of TCM properties.
Epidemiology and Outcomes of Neonatal Meningitis: Results of the Turkish Neo-Meningitis Nationwide Study
Authors: Oncel Mehmet Yekta , Cizmeci Mehmet N. , Karadag-Oncel Eda , Elvan-Tuz Aysegul , Canpolat Fuat Emre , Akin Mustafa Ali , Uslu Sinan , Cetinkaya Merih , Erdeve Omer , Koc Esin ,   the Neo-Meningitis Study Group
Published: December 2023

Objective:

To investigate the incidence and etiology of neonatal meningitis and to assess the associated risk factors, complications and outcomes in a nationwide multicenter retrospective descriptive study.

Method:

Twenty-seven centers from 7 geographical regions participated in the study. Newborns with a positive cerebrospinal fluid culture and/or cerebrospinal fluid polymerase chain reaction were included in the study. Demographic characteristics, clinical, laboratory and neuroimaging findings and mortality characteristics were analyzed.

Results:

A total of 634 confirmed cases of neonatal meningitis were included in the final analysis. The incidence was 2.51 per 1000 intensive care unit hospitalizations and mortality was observed in 149 (23.5%). Gram-positive bacteria were the predominant pathogens (54.5%), with coagulase-negative Staphylococci accounting for 45.3% of the cases, followed by Gram-negative organisms (37.3%). Viral and fungal organisms were isolated in 3.2% and 1.7% of the infants, respectively. Gram-negative culture growth was more common in infants who died (51% vs. 34.6%; P < 0.001). In the multivariable model, the odds of mortality was higher in those with respiratory distress requiring invasive ventilatory support [odds ratio (OR): 10.3; 95% confidence interval (CI): 4.9–21.7; P < 0.01], hypotension requiring inotropes (OR: 4.4; 95% CI: 2.7–7.1; P < 0.001), low birth weight status (OR: 2.5; 95% CI: 1.4–4.6; P = 0.002), lack of exposure to antenatal steroids (OR: 2.4; 95% CI: 1.3–4.4; P = 0.005) and the presence of concomitant sepsis (OR: 1.9; 95% CI: 1.1–3.2; P = 0.017).

Conclusions:

In this nationwide study, neonatal meningitis was found to be associated with high mortality. Coagulase-negative Staphylococci was the most common causative microorganism followed by Gram-negative bacteria. Severe clinical presentation with invasive mechanical ventilation and inotrope requirement, as well as concomitant sepsis, low birth weight status and lack of exposure to antenatal steroids, were found to be independent risk factors for mortality.
Fatal Oedipism: A Case Report and Literature Review
Authors: Gupta Lalita , Houchens Tucker , Khair Diana , Hughes Samuel , Vora Paras , Zoerner Douglas , Fraser Justin , Timoney Peter J.
Published: December 2023

Purpose:

To describe a unique case of a fatal self-enucleation and review previously published cases.

Methods:

The authors describe a unique case of a complete unilateral self-enucleation while under the influence of drugs, which resulted in severe intracranial hemorrhages, right internal carotid artery opacification, and death. A literature review was performed by searching articles published before January 2023 in the Pubmed/MEDLINE database using the keywords “auto-enucleation or self-enucleation.” Cases of self-inflicted damage to the globe without severing any connections were excluded.

Results:

A literature review identified a total of 54 articles and 75 patients who had self-enucleated at least one globe completely (84.0%). Their average age was 37 years and 50.7% were male. At the time of auto-enucleation, 64.0% of these patients had known psychiatric disorders, and 28.0% were found to be under the influence of illicit drugs or alcohol. Auto-enucleation resulted in intracranial complications in 26.7% of cases. There has been 1 prior case, which, like the authors’ case, resulted in death due to intracranial complications. However, this occurred in a patient who partially enucleated one eye after a self-inflicted injury to the fellow eye. The current case is unique as these complications resulted from a complete unilateral auto-enucleation.

Conclusions:

The severity of this case’s presentation and outcome highlights the importance of prompt neuroimaging and a thorough assessment. Prompt psychiatric assessment and treatment are also required.
Long-Term Outcome of Staged Socket Surgery for Acquired Anophthalmos
Authors: Vahdani Kaveh , Rose Geoffrey E. , Ortiz-Pérez S. , Verity D. H.
Published: December 2023

Purpose:

To evaluate long-term outcomes of staged volume rehabilitation for acquired anophthalmos.

Methods:

Case-note review of patients who had preceding i) eye removal without implant, ii) eye removal with an intraconal implant, but ball-related problems, or iii) removal of exposed implant. Secondary interventions were a) a first-time ball implant, b) dermis-fat graft, c) ball repositioning, d) ball replacement after prior removal, or e) orbital floor implantation.

Results:

Secondary volume-augmenting surgery was performed in 175 sockets at a mean age of 42.7 years (range 2–91), with 62% secondary ball implants, 3% dermis-fat grafts, 6% ball repositioning, 19% ball replacement after prior removal for exposure, and 10% having orbital floor implantation. After this surgery, further volume enhancement was required in 21% of sockets, this being 40% for spheres ≤18 mm diameter, in contrast to 6% for those ≥20 mm (p < 0.001). Exposure or malposition of the secondary implant occurred in 8% (12/151) and was unrelated to implant type, size, wrapping, or prior irradiation. Tertiary surgery addressed lining deficiency (18%) or eyelid malposition (25%). Overall, 92/175 (53%) had tertiary surgery to improve cosmesis and comfort, with 49% (36/92) being related to small implants. At a mean follow-up of 9.1 years, 82% of sockets had adequate volume, 79% had excellent lining, and 93% were comfortable. Prosthetic fit was satisfactory in 96% of cases, and 97% reported improved cosmesis.

Conclusion:

Over half of the sockets having planned 2-stage volume enhancement may need further procedures, especially after small-volume secondary implants, but, with meticulous surgery, reasonable long-term results can be achieved with few complications.
Applications of the pinhole effect in clinical vision science
Authors: Kanclerz Piotr , Khoramnia Ramin , Atchison David
Published: December 2023

The pinhole effect is commonly used to discriminate uncorrected refractive error from ocular diseases. A small aperture limits the width of light beams entering the eye, thus increasing the depth of focus. The pinhole effect has also been used in spectacles, contact lenses, corneal inlays, and intraocular lenses (IOLs) to improve reading by compensating for loss of accommodative function. Pinhole spectacles improve near visual acuity, but reduce reading speed, increase interblink interval, and decrease tear break-up time. For contact lenses and IOLs, pinhole devices are usually used in the nondominant eye, which allow compensation of various refractive errors and decrease spectacle dependence. Pinhole corneal inlays are implanted during laser in situ keratomileusis or as a separate procedure. Pinhole IOLs are gaining popularity, particularly as they do not bring a risk of a local inflammatory reaction as corneal inlays do. Disadvantages of using the pinhole effect include high susceptibility to decentration, decrease in retinal luminance levels, and difficulties in performing fundus examinations or surgery in eyes with implanted devices. There are also concerns regarding perceptive issues with different retinal illuminances in the 2 eyes (the Pulfrich effect).
Effect of exposure-based vs traditional cognitive behavior therapy for fibromyalgia: a two-site single-blind randomized controlled trial
Authors: Hedman-Lagerlöf Maria , Gasslander Nils , Ahnlund Hoffmann Alice , Bragesjö Maria , Etzell Amanda , Ezra Simon , Frostell Elsa , Hedman-Lagerlöf Erik , Ivert Caroline , Liliequist Björn , Ljótsson Brjánn , Hoppe Johanna M. , Palmgren Josefin , Spansk Edward , Sundström Felicia , Särnholm Josefin , Tzavara Georgia , Buhrman Monica , Axelsson Erland
Published: December 2023

Fibromyalgia is a debilitating pain condition for which treatment effects are typically modest. The most evaluated psychological treatment is traditional cognitive behavior therapy (T-CBT), but promising effects have recently been seen in exposure-based cognitive behavior therapy (Exp-CBT). We investigated whether Exp-CBT was superior to T-CBT in a randomized controlled trial. Self-referred participants with fibromyalgia (N = 274) were randomized (1:1) to 10 weeks of Exp-CBT or T-CBT. Treatments were delivered online and presented as “CBT for fibromyalgia.” Participants were assessed at baseline, weekly during treatment, posttreatment, and at 6- and 12-month follow-up. Primary outcome was the difference in reduction in fibromyalgia severity as measured using the Fibromyalgia Impact Questionnaire (FIQ) over 11 assessment points from baseline to posttreatment, modelled within an intention-to-treat framework using linear mixed effects models fitted on multiple imputed data. Approximately 91% of weekly FIQ scores were collected over the main phase. There was no significant difference between Exp-CBT and T-CBT in the mean reduction of fibromyalgia severity from pretreatment to posttreatment (b = 1.3, 95% CI −3.0 to 5.7, P = 0.544, d = −0.10). Minimal clinically important improvement was seen 60% in Exp-CBT vs 59% in T-CBT. Effects were sustained up to 12 months posttreatment. This well-powered randomized trial indicated that Exp-CBT was not superior to T-CBT for fibromyalgia. Both treatments were associated with a marked reduction in fibromyalgia severity, and the online treatment format might be of high clinical utility. T-CBT can still be regarded a reference standard treatment that remains clinically relevant when compared to novel treatment approaches.
The impact of diabetes on overactive bladder presentations and associations with health-seeking behavior in China, South Korea, and Taiwan: Results from a cross-sectional, population-based study
Authors: Lee Wei-Chia , Chow Po-Ming , Hsu Chien-Ning , Chuang Yao-Chi
Published: December 2023

Background:

This study aimed to explore the impact of diabetes on overactive bladder (OAB) presentations and related predictors of healthcare-seeking behavior among adults aged ≥ 40 years in China, Taiwan, and South Korea.

Methods:

An internet-based survey was conducted to assess the prevalence of diabetes, OAB presentations, and self-perceived urinary symptoms by a multi-national sample of 8284 individuals who completed the survey between June 2, 2015 and July 31, 2015. Independent associations with health-seeking behavior for urinary symptoms were estimated with odds ratio (OR) with 95% confidence interval (95% CI) using multivariate logistic regression.

Results:

Diabetes was reported in 13.6% of participants and OAB was 20.8%. Diabetic participants were older than non-diabetic participants in both sexes. Participants with diabetes reported a higher rate of OAB (43.1%) and increased bothersome symptoms associated with OAB than those without diabetes. Participants with diabetes (OR, 3.07 [2.39-3.96]], urgent incontinence (OR, 2.38 [1.86-3.03]), frequency (OR, 1.86 [1.45-2.38]), and nocturia (OR, 1.14 [1.05-1.24]) were associated with healthcare-seeking behavior.

Conclusion:

The proportion of diabetic participants with OAB was 2.5-fold higher than those without diabetes. Diabetes, urinary frequency, nocturia, and urgent incontinence are predictors of medical treatment-seeking behavior, but the key symptom of OAB-urgency is not a predictor of treatment-seeking behavior. It is important for clinicians to recognize the interplay between diabetes and OAB and to early identify various bothersome urinary symptoms for better health outcomes in daily practice.
A Retrospective Analysis of Major League Baseball Hit-by-Pitch Rates before and after the Crackdown on Foreign Substance Use
Authors: Sitton Zachary , Swisher Jeremy , Davis Stephen , Thornton Heath
Published: December 2023

Objective:

Determine whether there was an increased incidence of hit-by-pitch events in Major League Baseball (MLB) following the decision to enforce the foreign substance ban for pitchers during the 2021 season.

Design:

Descriptive Epidemiological Study.

Setting:

Major League Baseball hit-by-pitch data from publicly available Web sites (mlb.com and fangraphs.com).

Participants:

Major League Baseball players during the 2017, 2018, 2019, 2021, and 2022 seasons.

Independent Variables:

Hit-by-pitch exposure data by season and individual pitch type.

Main Outcome Measures:

Hit-by-pitch incidence rates from the 2017 to 2019 seasons (preenforcement) and the 2021 to 2022 seasons (postenforcement). Rates were compared with incidence rate ratios (IRRs).

Results:

Hit-by-pitch incidence rate increased from 2.66 to 3.06 per 1000 total pitches (IRR, 1.15 [95% CI, 1.08-1.23]; P < 0.0001) following the enforcement. Incidence rates for 2017, 2018, and 2019 did not differ from each other individually, but incidence rate of all 3 seasons individually were significantly lower than that for the 2021 season (P < 0.005). Sliders were 29% more likely to hit batters following the enforcement (P = 0.0015).

Conclusions:

Major League Baseball batters were hit by pitches at a significantly higher rate following the league's crackdown on foreign substance use for the 2021 seasons compared with the same time of year during the 2017 to 2019 seasons. This was followed by a slight regression toward preenforcement levels during the 2022 season.
Impact of Playing Surface on Concussion Symptoms in Young American Football Players
Authors: Heinzelmann Morgan Michelle , Stokes Mathew , Miller Shane M. , Bunt Stephen C. , Hynan Linda S. , Didehbani Nyaz , Cullum C. Munro
Published: December 2023

Objective:

It has been suggested that sport-related concussion (SRC) occurs more commonly on natural grass compared with artificial turf in contact sports. As playing surface is a potentially modifiable risk factor, this study sought to identify differences in symptoms following SRC on these 2 surfaces in a sample of young American football players.

Design:

Prospective.

Setting:

Part of the multi-institutional North Texas Concussion Registry (ConTex) research project.

Participants:

Ten-year-old to 24-year-old male American football players (n = 62) who had sustained a helmet-to-ground SRC and presented to a specialty concussion clinic within 14 days of injury.

Independent Variables:

Helmeted impact with grass (n = 33) or artificial turf (n = 29).

Main Outcome Measures:

Severity and number of symptoms endorsed on the Sport Concussion Assessment Tool 5th Edition (SCAT5) Symptom Evaluation at the time of initial clinical evaluation.

Results:

Both groups were similar in mean time since injury, concussion history, and history of headache, but the artificial turf group was slightly older, with a mean age of 14.6 versus 13.6 years (P = 0.039). Athletes who sustained a SRC on grass reported significantly higher mean total symptom severity scores (26.6 vs 11.6, P = 0.005) and total number of symptoms (10.3 vs 5.9, P = 0.006) compared with those who were injured on artificial turf.

Conclusions:

This may be the first study to examine postconcussive symptoms after SRC as they relate to playing surface. This small sample of young American football players reported higher symptom severity scores and higher total number of symptoms after SRC on natural grass compared with artificial turf.