bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole exome sequencing revealed variants in four genes underlying X-linked intellectual disability in four Iranian families: novel deleterious variants and clinical features with the review of literature
Authors: Mir Atefeh , Song Yongjun , Lee Hane , Khanahmad Hossein , Khorram Erfan , Nasiri Jafar , Tabatabaiefar Mohammad Amin 
Published: October 2023

Abstract

Aim and Objective
Intellectual disability (ID) is a heterogeneous condition affecting brain development, function, and/or structure. The X-linked mode of inheritance of ID (X-linked intellectual disability; XLID) has a prevalence of 1 out of 600 to 1000 males. In the last decades, exome sequencing technology has revolutionized the process of disease-causing gene discovery in XLIDs. Nevertheless, so many of them still remain with unknown etiology. This study investigated four families with severe XLID to identify deleterious variants for possible diagnostics and prevention aims.

Methods
Nine male patients belonging to four pedigrees were included in this study. The patients were studied genetically for Fragile X syndrome, followed by whole exome sequencing and analysis of intellectual disability-related genes variants. Sanger sequencing, co-segregation analysis, structural modeling, and in silico analysis were done to verify the causative variants. In addition, we collected data from previous studies to compare and situate our work with existing knowledge.

Results
In three of four families, novel deleterious variants have been identified in three different genes, including ZDHHC9 (p. Leu189Pro), ATP2B3 (p. Asp847Glu), and GLRA2 (p. Arg350Cys) and also with new clinical features and in another one family, a reported pathogenic variant in the L1CAM (p. Glu309Lys) gene has been identified related to new clinical findings.

Conclusion
The current study's findings expand the existing knowledge of variants of the genes implicated in XLID and broaden the spectrum of phenotypes associated with the related conditions. The data have implications for genetic diagnosis and counseling.
Nanobody-based pannexin1 channel inhibitors reduce inflammation in acute liver injury
Authors: Van Campenhout Raf , De Groof Timo W. M. , Kadam Prashant , Kwak Brenda R. , Muyldermans Serge , Devoogdt Nick , Vinken Mathieu 
Published: October 2023

Abstract
Background
The opening of pannexin1 channels is considered as a key event in inflammation. Pannexin1 channel-mediated release of adenosine triphosphate triggers inflammasome signaling and activation of immune cells. By doing so, pannexin1 channels play an important role in several inflammatory diseases. Although pannexin1 channel inhibition could represent a novel clinical strategy for treatment of inflammatory disorders, therapeutic pannexin1 channel targeting is impeded by the lack of specific, potent and/or in vivo-applicable inhibitors. The goal of this study is to generate nanobody-based inhibitors of pannexin1 channels.

Results
Pannexin1-targeting nanobodies were developed as potential new pannexin1 channel inhibitors. We identified 3 cross-reactive nanobodies that showed affinity for both murine and human pannexin1 proteins. Flow cytometry experiments revealed binding capacities in the nanomolar range. Moreover, the pannexin1-targeting nanobodies were found to block pannexin1 channel-mediated release of adenosine triphosphate. The pannexin1-targeting nanobodies were also demonstrated to display anti-inflammatory effects in vitro through reduction of interleukin 1 beta amounts. This anti-inflammatory outcome was reproduced in vivo using a human-relevant mouse model of acute liver disease relying on acetaminophen overdosing. More specifically, the pannexin1-targeting nanobodies lowered serum levels of inflammatory cytokines and diminished liver damage. These effects were linked with alteration of the expression of several NLRP3 inflammasome components.

Conclusions
This study introduced for the first time specific, potent and in vivo-applicable nanobody-based inhibitors of pannexin1 channels. As demonstrated for the case of liver disease, the pannexin1-targeting nanobodies hold great promise as anti-inflammatory agents, yet this should be further tested for extrahepatic inflammatory disorders. Moreover, the pannexin1-targeting nanobodies represent novel tools for fundamental research regarding the role of pannexin1 channels in pathological and physiological processes.

Graphical Abstract
Construction of a predictive model for osteoporosis risk in men: using the IOF 1-min osteoporosis test
Authors: Zhang Kun , Wang Min , Han Weidong , Yi Weihong , Yang Dazhi 
Published: October 2023

Abstract
Objective
To construct a clinical prediction nomogram model using the 1-min IOF osteoporosis risk test as an evaluation tool for male osteoporosis.

Methods
The 1-min test results and the incidence of osteoporosis were collected from 354 patients in the osteoporotic clinic of our hospital. LASSO regression model and multi-factor logistic regression were used to analyze the risk factors of osteoporosis in patients, and the risk prediction model of osteoporosis was established. Verify with an additional 140 objects.

Results
We used logistic regression to construct a nomogram model. According to the model, the AUC value of the training set was 0.760 (0.704–0.817). The validation set has an AUC value of 0.806 (0.733–0.879). The test set AUC value is 0.714 (0.609–0.818). The calibration curve shows that its advantage is that the deviation correction curve of the nomogram model can maintain a good consistency with the ideal curve. In terms of clinical applicability, compared with the "total intervention" and "no intervention" schemes, the clinical net return rate of the nomogram model showed certain advantages.

Conclusion
Using the 1-min osteoporosis risk test provided by IOF, we built a male osteoporosis risk prediction model with good prediction effect, which can provide greater reference and help for clinicians.
Age-related changes in neural responses to sensory stimulation in autism: a cross-sectional study
Authors: Cakar Melis E. , Cummings Kaitlin K. , Bookheimer Susan Y. , Dapretto Mirella , Green Shulamite A. 
Published: October 2023

Abstract
Background
Sensory over-responsivity (SOR) is an impairing sensory processing challenge in autism spectrum disorder (ASD) which shows heterogenous developmental trajectories and appears to improve into adulthood in some but not all autistic individuals. However, the neural mechanisms underlying interindividual differences in these trajectories are currently unknown.

Methods
Here, we used functional magnetic resonance imaging (fMRI) to investigate the association between age and neural activity linearly and nonlinearly in response to mildly aversive sensory stimulation as well as how SOR severity moderates this association. Participants included 52 ASD (14F) and 41 (13F) typically developing (TD) youth, aged 8.6–18.0 years.

Results
We found that in pre-teens, ASD children showed widespread activation differences in sensorimotor, frontal and cerebellar regions compared to TD children, while there were fewer differences between ASD and TD teens. In TD youth, older age was associated with less activation in the prefrontal cortex. In contrast, in ASD youth, older age was associated with more engagement of sensory integration and emotion regulation regions. In particular, orbitofrontal and medial prefrontal cortices showed a nonlinear relationship with age in ASD, with an especially steep increase in sensory-evoked neural activity during the mid-to-late teen years. There was also an interaction between age and SOR severity in ASD youth such that these age-related trends were more apparent in youth with higher SOR.

Limitations
The cross-sectional design limits causal interpretations of the data. Future longitudinal studies will be instrumental in determining how prefrontal engagement and SOR co-develop across adolescence.

Conclusions
Our results suggest that enhanced recruitment of prefrontal regions may underlie age-related decreases in SOR for a subgroup of ASD youth.
Surgical technique of spine-shortening vertebral osteotomy for adult tethered cord syndrome: a case report and review of the literature
Authors: Kobayashi Takashi , Miyakoshi Naohisa , Abe Toshiki , Kikuchi Kazuma , Abe Eiji , Shimada Yoichi 
Published: October 2023

Abstract
Background
Miyakoshi et al. reported three cases of tethered cord syndrome treated by spine-shortening vertebral osteotomy, which provided relief of the patients’ symptoms with no complications. Although the details of these cases were described in a previous report, the surgical technique was not thoroughly explained. In the present report, we describe the details of our procedure with reference to a fourth case.

Case presentation
A 47-year-old Asian woman was admitted to our hospital with a 1-year history of worsening leg numbness and urinary dysfunction. Magnetic resonance imaging revealed a low-lying conus medullaris extending to the level of S2 and surrounded by fat tissue at that level. We diagnosed her condition as adult tethered cord syndrome, and spine-shortening vertebral osteotomy was planned. The target level for the osteotomy was L2. Bilateral pedicle screw implants were placed at L1 and L3 using an anterior–posterior image intensifier. In this procedure, it is essential to use monoaxial screws inserted exactly parallel to the rostral endplates of each vertebral body; this ensures appropriate alignment between the L1 caudal endplate and the L2 osteotomy surface. The upper one-third of the lamina of L2 was resected, and the bilateral two-thirds of the pedicle of L2 was removed with a surgical air drill. After exposure of the lateral side of the L1–2 disc, discectomy was performed with a knife and curette. Following complete discectomy of L1–2, the upper vertebral body of L2 was removed with a surgical air drill. After complete removal of the vertebral body, a straight rod was connected to two screws and applied pressure between the screws. Two polyethylene tapes were applied to the L2 lamina and bilateral rods.

Conclusion
Spine-shortening osteotomy that preserves the caudal one-third of the pedicle and lamina with one-above and one-below instrumentation successfully reduced the spinal cord tension without causing neural damage.
The relationship between the level of NMLR on admission and the prognosis of patients after cardiopulmonary resuscitation: a retrospective observational study
Authors: Lin Qingting , Zhang Nan , Zhu Huadong 
Published: October 2023

Abstract
Background
The inflammatory immune response is involved in the pathophysiology of the post-cardiac arrest syndrome and leads to high mortality. The admission (neutrophil + monocyte) to lymphocyte ratio (NMLR) can help us to assess the immune inflammatory status of patients. We aimed to identify factors that affect the prognosis and explore the association between NMLR and the prognosis of patients after cardiopulmonary resuscitation (CPR).

Methods
This is a retrospective study based on the MIMIC-IV database. We assessed patients admitted to the ICU after cardiopulmonary resuscitation, included demographic characteristics, peripheral blood cell count and blood gas indicators for the first time after admission to the ICU, developed a multivariate COX proportional-hazards model to explore prognostic factors, and divided patients into High NMLR and Low NMLR groups by cutoff values of NMLR. Propensity score matching (PSM) was used to adjust confounding factors.

Results
A total of 955 patients were included in the analysis, with 497 surviving and 458 dying during the follow-up period. In a multivariate Cox proportional-hazards model, age (RR 1.007, p = 0.0411), NMLR levels (RR 1.003, p = 0.0381), lactate (RR 1.097, p < 0.001) and hematocrit (RR 1.101, p < 0.001) were independent risk factors for patient death following CPR. Patients were divided into a high NMLR group (> 14.2) and a low NMLR group (≤ 14.2) based on the optimal threshold for NMLR. Compared to low NMLR group, high NMLR group had higher total vasoactive drugs and lower 28-day survival. After PSM, there were no differences in baseline characteristics. The high NMLR group still had a higher mortality rate (p = 0.001), lower 28-day survival (p = 0.001) and shorter length of stay (p = 0.005) compared to the low NMLR group.

Conclusions
Age, NMLR levels, lactate levels and hematocrit were independent risk factors for death in patients after CPR. NMLR > 14.2 was associated with higher mortality and was a potential predictor of clinical outcome in patients after CPR.
From nitrate to NO: potential effects of nitrate-reducing bacteria on systemic health and disease
Authors: Liu Hongyu , Huang Yisheng , Huang Mingshu , Wang Min , Ming Yue , Chen Weixing , Chen Yuanxin , Tang Zhengming , Jia Bo 
Published: October 2023

AbstractCurrent research has described improving multisystem disease and organ function through dietary nitrate (DN) supplementation. They have provided some evidence that these floras with nitrate (NO3−) reductase are mediators of the underlying mechanism. Symbiotic bacteria with nitrate reductase activity (NRA) are found in the human digestive tract, including the mouth, esophagus and gastrointestinal tract (GT). Nitrate in food can be converted to nitrite under the tongue or in the stomach by these symbiotic bacteria. Then, nitrite is transformed to nitric oxide (NO) by non-enzymatic synthesis. NO is currently recognized as a potent bioactive agent with biological activities, such as vasodilation, regulation of cardiomyocyte function, neurotransmission, suppression of platelet agglutination, and prevention of vascular smooth muscle cell proliferation. NO also can be produced through the conventional l-arginine–NO synthase (l-NOS) pathway, whereas endogenous NO production by l-arginine is inhibited under hypoxia–ischemia or disease conditions. In contrast, exogenous NO3−/NO2−/NO activity is enhanced and becomes a practical supplemental pathway for NO in the body, playing an essential role in various physiological activities. Moreover, many diseases (such as metabolic or geriatric diseases) are primarily associated with disorders of endogenous NO synthesis, and NO generation from the exogenous NO3−/NO2−/NO route can partially alleviate the disease progression. The imbalance of NO in the body may be one of the potential mechanisms of disease development. Therefore, the impact of these floras with nitrate reductase on host systemic health through exogenous NO3−/NO2−/NO pathway production of NO or direct regulation of floras ecological balance is essential (e.g., regulation of body homeostasis, amelioration of diseases, etc.). This review summarizes the bacteria with nitrate reductase in humans, emphasizing the relationship between the metabolic processes of this microflora and host systemic health and disease. The potential effects of nitrate reduction bacteria on human health and disease were also highlighted in disease models from different human systems, including digestive, cardiovascular, endocrine, nervous, respiratory, and urinary systems, providing innovative ideas for future disease diagnosis and treatment based on nitrate reduction bacteria.
Identification of predictive biomarkers for endometrial cancer diagnosis and treatment response monitoring using plasma metabolome profiling
Authors: Hishinuma Eiji , Shimada Muneaki , Matsukawa Naomi , Shima Yoshiko , Li Bin , Motoike Ikuko N. , Shibuya Yusuke , Hagihara Tatsuya , Shigeta Shogo , Tokunaga Hideki , Saigusa Daisuke , Kinoshita Kengo , Koshiba Seizo , Yaegashi Nobuo 
Published: October 2023

Abstract
Background
Endometrial cancer (EMC) is the most common female genital tract malignancy with an increasing prevalence in many countries including Japan, a fact that renders early detection and treatment necessary to protect health and fertility. Although early detection and treatment are necessary to further improve the prognosis of women with endometrial cancer, biomarkers that accurately reflect the pathophysiology of EMC patients are still unclear. Therefore, it is clinically critical to identify biomarkers to assess diagnosis and treatment efficacy to facilitate appropriate treatment and development of new therapies for EMC.

Methods
In this study, wide-targeted plasma metabolome analysis was performed to identify biomarkers for EMC diagnosis and the prediction of treatment responses. The absolute quantification of 628 metabolites in plasma samples from 142 patients with EMC was performed using ultra-high-performance liquid chromatography with tandem mass spectrometry.

Results
The concentrations of 111 metabolites increased significantly, while the concentrations of 148 metabolites decreased significantly in patients with EMC compared to healthy controls. Specifically, LysoPC and TGs, including unsaturated fatty acids, were reduced in patients with stage IA EMC compared to healthy controls, indicating that these metabolic profiles could be used as early diagnostic markers of EMC. In contrast, blood levels of amino acids such as histidine and tryptophan decreased as the risk of recurrence increased and the stages of EMC advanced. Furthermore, a marked increase in total TG and a decrease in specific TGs and free fatty acids including polyunsaturated fatty acids levels were observed in patients with EMC. These results suggest that the polyunsaturated fatty acids in patients with EMC are crucial for disease progression.

Conclusions
Our data identified specific metabolite profiles that reflect the pathogenesis of EMC and showed that these metabolites correlate with the risk of recurrence and disease stage. Analysis of changes in plasma metabolite profiles could be applied for the early diagnosis and monitoring of the course of treatment of EMC patients.
Solving multiphysics-based inverse problems with learned surrogates and constraints
Authors: Yin Ziyi , Orozco Rafael , Louboutin Mathias , Herrmann Felix J. 
Published: October 2023

AbstractSolving multiphysics-based inverse problems for geological carbon storage monitoring can be challenging when multimodal time-lapse data are expensive to collect and costly to simulate numerically. We overcome these challenges by combining computationally cheap learned surrogates with learned constraints. Not only does this combination lead to vastly improved inversions for the important fluid-flow property, permeability, it also provides a natural platform for inverting multimodal data including well measurements and active-source time-lapse seismic data. By adding a learned constraint, we arrive at a computationally feasible inversion approach that remains accurate. This is accomplished by including a trained deep neural network, known as a normalizing flow, which forces the model iterates to remain in-distribution, thereby safeguarding the accuracy of trained Fourier neural operators that act as surrogates for the computationally expensive multiphase flow simulations involving partial differential equation solves. By means of carefully selected experiments, centered around the problem of geological carbon storage, we demonstrate the efficacy of the proposed constrained optimization method on two different data modalities, namely time-lapse well and time-lapse seismic data. While permeability inversions from both these two modalities have their pluses and minuses, their joint inversion benefits from either, yielding valuable superior permeability inversions and CO2 plume predictions near, and far away, from the monitoring wells.
Connecting community’s perspectives on tsunami risk to anticipated future tsunamis: a reflection from a progress of tsunami preparedness from a coastal community in Aceh-Indonesia after 19 years of the 2004 Indian Ocean Tsunami
Authors: Benazir  , Syamsidik  , Idris Yunita , Putra Nadri Pratama 
Published: October 2023

AbstractThis paper reflects on the progress of tsunami preparedness in a coastal community in Aceh, Indonesia, nearly two decades after the catastrophic 2004 Indian Ocean Tsunami. The research employs a comprehensive approach to thoroughly evaluate and comprehend the community’s preparedness, its correlation with local perceptions of tsunami risk, and delves into the prevalence of tsunamis in the area, with a specific emphasis on the significant impact of the 2004 Indian Ocean Tsunami on the coastal community of Aceh. To investigate the community’s readiness and the potential impacts of tsunamis at the study site, tsunami simulations were performed using the shallow water equation within the COMCOT (Cornell Multi-grid Coupled Tsunami) model. These simulations assessed run-up and inundation scenarios, thereby providing justification for the potential tsunami impact in the area. Modelling the scenario of tsunami in the region is important to measure the potential impact and estimation time for community to prepare the evacuation plan. In addition to the numerical modeling, a mixed-method approach was employed, involving the distribution of questionnaires and conducting in-depth interviews with 150 respondents directly on-site. These assessments yielded valuable insights into community perspectives on tsunami risk and their preparedness measures. The findings contribute to the development of effective strategies for disaster management by integrating local knowledge, experiences, and socialization programs. The study emphasizes the significance of ongoing endeavors to enhance community preparedness and mitigate the consequences of tsunamis.
A stakeholder-developed logic model to improve utilization of pharmacy-prescribed contraception in Utah
Authors: Simmons Rebecca G. , Baayd Jami , Tak Casey , Turok David K. , Elliott Sarah , Smith Justin D. 
Published: October 2023

Abstract
Background
Currently, 20 states in the USA have passed policies allowing pharmacists to prescribe short-acting hormonal contraception, including pills, patches, and vaginal rings. Yet, utilization of these services remains limited. The purpose of this study was to (a) assess barriers and facilitators of pharmacy contraceptive dispensing among contraceptive users, pharmacists, and healthcare providers in Utah and (b) adapt and propose an evidence-based contraceptive intervention in the pharmacy environment.

Methods
We conducted 6 focus groups among contraceptive users, pharmacists, and healthcare providers assessing current barriers and facilitators to pharmacy prescribing. We coded transcripts of these focus groups to the Consolidated Framework for Implementation Research, Version 2.0 (CFIR) and characterized the findings based on the Expert Recommendations for Implementing Change (ERIC) Barrier-Busting tool. Based on the CFIR findings and ERIC strategies output, we adapted an existing evidence-based intervention (a contraceptive access initiative) to the Utah pharmacy environment. We then convened a pharmacy stakeholder meeting and presented elements of an Implementation Research Logic Model and obtained feedback. We coded this feedback to the CFIR framework to finalize an Implementation Research Logic Model for a proposed implementation approach to improving contraceptive prescribing.

Results
Initial focus group responses clustered around specific implementation barriers including financial barriers (cost for patients, as well as lack of reimbursement for pharmacist’s time); lack of awareness of the service (on the part of patients, pharmacists, and health care providers); need for updated tools for contraceptive counseling and scheduling; and need for increased pharmacists education to conduct contraceptive counseling. Proposed adaptations to the existing contraceptive access intervention included development of a technology-based patient/pharmacist screener tool and a healthcare provider/pharmacist contraceptive referral network. Stakeholders identified pharmacist reimbursement as the top priority for improving utilization.

Conclusions
Elements of contraceptive access initiatives mapped well as proposed implementation strategies to improving utilization of contraceptive prescribing in pharmacies.