bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis for pathogenic variants of GJB2 and hearing levels of patients with hearing loss
Authors: Namba Kazunori , Mutai Hideki , Matsunaga Tatsuo , Kaneko Hiroki 
Published: May 2024

Abstract
Objectives
The crystal structure of the six protomers of gap junction protein beta 2 (GJB2) enables prediction of the effect(s) of an amino acid substitution, thereby facilitating investigation of molecular pathogenesis of missense variants of GJB2. This study mainly focused on R143W variant that causes hearing loss, and investigated the relationship between amino acid substitution and 3-D structural changes in GJB2.

Methods
Patients with nonsyndromic hearing loss who appeared to have two GJB2 pathogenic variants, including the R143W variant, were investigated. Because the X-ray crystal structure of the six protomers of the GJB2 protein is known, R143W and structurally related variants of GJB2 were modeled using this crystal structure as a template. The wild-type crystal structure and the variant computer-aided model were observed and the differences in molecular interactions within the two were analyzed.

Results
The predicted structure demonstrated that the hydrogen bond between R143 and N206 was important for the stability of the protomer structure. From this prediction, R143W related N206S and N206T variants showed loss of the hydrogen bond.

Conclusion
Investigation of the genotypes and clinical data in patients carrying the R143W variant on an allele indicated that severity of hearing loss depends largely on the levels of dysfunction of the pathogenic variant on the allele, whereas a patient with the homozygous R143W variant demonstrated profound hearing loss. We concluded that these hearing impairments may be due to destabilization of the protomer structure of GJB2 caused by the R143W variant.
Cerebrospinal fluid α-synuclein adds the risk of cognitive decline and is associated with tau pathology among non-demented older adults
Authors: Liu Wenying , Li Wenwen , Liu Zhaojun , Li Yan , Wang Xuechu , Guo Mengmeng , Wang Shiyuan , Wang Shuheng , Li Yan , Jia Jianping 
Published: May 2024

Abstract
Background
The role of α-synuclein in dementia has been recognized, yet its exact influence on cognitive decline in non-demented older adults is still not fully understood.

Methods
A total of 331 non-demented individuals were included in the study from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Participants were divided into two distinct groups based on their α-synuclein levels: one with lower levels (α-synuclein-L) and another with higher levels (α-synuclein-H). Measurements included neuropsychiatric scales, cerebrospinal fluid (CSF) biomarkers, and blood transcriptomics. The linear mixed-effects model investigated the longitudinal changes in cognition. Kaplan-Meier survival analysis and the Cox proportional hazards model were utilized to evaluate the effects of different levels of α-synuclein on dementia. Gene set enrichment analysis (GSEA) was utilized to investigate the biological pathways related to cognitive impairment. Pearson correlation, multiple linear regression models, and mediation analysis were employed to investigate the relationship between α-synuclein and neurodegenerative biomarkers, and their potential mechanisms affecting cognition.

Results
Higher CSF α-synuclein levels were associated with increased risk of cognitive decline and progression to dementia. Enrichment analysis highlighted the activation of tau-associated and immune response pathways in the α-synuclein-H group. Further correlation and regression analysis indicated that the CSF α-synuclein levels were positively correlated with CSF total tau (t-tau), phosphorylated tau (p-tau) 181, tumor necrosis factor receptor 1 (TNFR1) and intercellular cell adhesion molecule-1 (ICAM-1). Mediation analysis further elucidated that the detrimental effects of CSF α-synuclein on cognition were primarily mediated through CSF t-tau and p-tau. Additionally, it was observed that CSF α-synuclein influenced CSF t-tau and p-tau181 levels via inflammatory pathways involving CSF TNFR1 and ICAM-1.

Conclusions
These findings elucidate a significant connection between elevated levels of CSF α-synuclein and the progression of cognitive decline, highlighting the critical roles of activated inflammatory pathways and tau pathology in this association. They underscore the importance of monitoring CSF α-synuclein levels as a promising biomarker for identifying individuals at increased risk of cognitive deterioration and developing dementia.
Association between untreated and treated blood pressure levels and cognitive decline in community-dwelling middle-aged and older adults in China: a longitudinal study
Authors: Li Haibin , Wang Man , Qian Frank , Wu Zhiyuan , Liu Weida , Wang Anxin , Guo Xiuhua 
Published: May 2024

Abstract
Background
Optimal blood pressure (BP) levels to reduce the long-term risk of cognitive decline remains controversial. We aimed to investigate the association between BP and anti-hypertensive treatment status with cognitive decline in older adults.

Methods
This study used data from the China Health and Retirement Longitudinal Study. Cognitive function was assessed at year 2011, 2013, 2015, and 2018. Global cognitive Z-score was calculated as the average score of episodic memory and mental intactness. BP were measured at the first and second wave. Pulse pressure (PP) was calculated as systolic BP (SBP) minus diastolic BP. Cumulative BP was calculated as the area under the curve using BP measurements from 2011 to 2013. Linear mixed models were used to assess the longitudinal association between BP-related measurements and cognitive decline.

Results
We included 11,671 participants (47.3% men and mean age 58.6 years). Individual with BP > 140/90 mm Hg or taking anti-hypertensive medication were independently associated with accelerated cognitive decline (β=-0.014, 95% CI: -0.020 to -0.007). Individuals with anti-hypertensive medication use, but with controlled SBP to less than 120 mm Hg did not have a significantly increased risk of cognitive decline compared with normotension (β=-0.003, 95% CI: -0.021 to 0.014). Individuals on anti-hypertensive treatment with PP of more than 70 mm Hg had a significantly higher risk of cognitive decline (β=-0.033, 95% CI: -0.045 to -0.020). Regardless of anti-hypertensive treatment status, both elevated baseline and cumulative SBP and PP were found to be independently associated with accelerated cognitive decline.

Conclusions
Cumulatively elevated SBP, PP and uncontrolled BP were associated with subsequent cognitive decline. Effectively controlling BP with anti-hypertensive treatment may be able to preserve cognitive decline in older adults.
Proteo-transcriptomic profiles reveal key regulatory pathways and functions of LDHA in the ovulation of domestic chickens (Gallus gallus)
Authors: Nie Ruixue , Zhang Wenhui , Tian Haoyu , Li Junying , Ling Yao , Zhang Bo , Zhang Hao , Wu Changxin 
Published: May 2024

Abstract
Background
In poultry, the smooth transition of follicles from the preovulatory-to-postovulatory phase impacts egg production in hens and can benefit the poultry industry. However, the regulatory mechanism underlying follicular ovulation in avians is a complex biological process that remains unclear.

Results
Critical biochemical events involved in ovulation in domestic chickens (Gallus gallus) were evaluated by transcriptomics, proteomics, and in vitro assays. Comparative transcriptome analyses of the largest preovulatory follicle (F1) and postovulatory follicle (POF1) in continuous laying (CL) and intermittent laying (IL) chickens indicated the greatest difference between CL_F1 and IL_F1, with 950 differentially expressed genes (DEGs), and the smallest difference between CL_POF1 and IL_POF1, with 14 DEGs. Additionally, data-independent acquisition proteomics revealed 252 differentially abundant proteins between CL_F1 and IL_F1. Perivitelline membrane synthesis, steroid biosynthesis, lysosomes, and oxidative phosphorylation were identified as pivotal pathways contributing to ovulation regulation. In particular, the regulation of zona pellucida sperm-binding protein 3, plasminogen activator, cathepsin A, and lactate dehydrogenase A (LDHA) was shown to be essential for ovulation. Furthermore, the inhibition of LDHA decreased cell viability and promoted apoptosis of ovarian follicles in vitro.

Conclusions
This study reveals several important biochemical events involved in the process of ovulation, as well as crucial role of LDHA. These findings improve our understanding of ovulation and its regulatory mechanisms in avian species.
Gut microbiota, blood metabolites, and left ventricular diastolic dysfunction in US Hispanics/Latinos
Authors: Luo Kai , Taryn Alkis , Moon Eun-Hye , Peters Brandilyn A. , Solomon Scott D. , Daviglus Martha L. , Kansal Mayank M. , Thyagarajan Bharat , Gellman Marc D. , Cai Jianwen , Burk Robert D. , Knight Rob , Kaplan Robert C. , Cheng Susan , Rodriguez Carlos J. , Qi Qibin , Yu Bing 
Published: May 2024

Abstract
Background
Left ventricular diastolic dysfunction (LVDD) is an important precursor of heart failure (HF), but little is known about its relationship with gut dysbiosis and microbial-related metabolites. By leveraging the multi-omics data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a study with population at high burden of LVDD, we aimed to characterize gut microbiota associated with LVDD and identify metabolite signatures of gut dysbiosis and incident LVDD.

Results
We included up to 1996 Hispanic/Latino adults (mean age: 59.4 years; 67.1% female) with comprehensive echocardiography assessments, gut microbiome, and blood metabolome data. LVDD was defined through a composite criterion involving tissue Doppler assessment and left atrial volume index measurements. Among 1996 participants, 916 (45.9%) had prevalent LVDD, and 212 out of 594 participants without LVDD at baseline developed incident LVDD over a median 4.3 years of follow-up. Using multivariable-adjusted analysis of compositions of microbiomes (ANCOM-II) method, we identified 7 out of 512 dominant gut bacterial species (prevalence > 20%) associated with prevalent LVDD (FDR-q < 0.1), with inverse associations being found for Intestinimonas_massiliensis, Clostridium_phoceensis, and Bacteroide_coprocola and positive associations for Gardnerella_vaginali, Acidaminococcus_fermentans, Pseudomonas_aeruginosa, and Necropsobacter_massiliensis. Using multivariable adjusted linear regression, 220 out of 669 circulating metabolites with detection rate > 75% were associated with the identified LVDD-related bacterial species (FDR-q < 0.1), with the majority being linked to Intestinimonas_massiliensis, Clostridium_phoceensis, and Acidaminococcus_fermentans. Furthermore, 46 of these bacteria-associated metabolites, mostly glycerophospholipids, secondary bile acids, and amino acids, were associated with prevalent LVDD (FDR-q < 0.1), 21 of which were associated with incident LVDD (relative risk ranging from 0.81 [p = 0.001, for guanidinoacetate] to 1.25 [p = 9 × 10−5, for 1-stearoyl-2-arachidonoyl-GPE (18:0/20:4)]). The inclusion of these 21 bacterial-related metabolites significantly improved the prediction of incident LVDD compared with a traditional risk factor model (the area under the receiver operating characteristic curve [AUC] = 0.73 vs 0.70, p = 0.001). Metabolite-based proxy association analyses revealed the inverse associations of Intestinimonas_massilliensis and Clostridium_phoceensis and the positive association of Acidaminococcus_fermentans with incident LVDD.

Conclusion
In this study of US Hispanics/Latinos, we identified multiple gut bacteria and related metabolites linked to LVDD, suggesting their potential roles in this preclinical HF entity.
Co-localization of antibiotic resistance genes is widespread in the infant gut microbiome and associates with an immature gut microbial composition
Authors: Li Xuanji , Brejnrod Asker , Trivedi Urvish , Russel Jakob , Thorsen Jonathan , Shah Shiraz A , Vestergaard Gisle Alberg , Rasmussen Morten Arendt , Nesme Joseph , Bisgaard Hans , Stokholm Jakob , Sørensen Søren Johannes 
Published: May 2024

Abstract
Background
In environmental bacteria, the selective advantage of antibiotic resistance genes (ARGs) can be increased through co-localization with genes such as other ARGs, biocide resistance genes, metal resistance genes, and virulence genes (VGs). The gut microbiome of infants has been shown to contain numerous ARGs, however, co-localization related to ARGs is unknown during early life despite frequent exposures to biocides and metals from an early age.

Results
We conducted a comprehensive analysis of genetic co-localization of resistance genes in a cohort of 662 Danish children and examined the association between such co-localization and environmental factors as well as gut microbial maturation. Our study showed that co-localization of ARGs with other resistance and virulence genes is common in the early gut microbiome and is associated with gut bacteria that are indicative of low maturity. Statistical models showed that co-localization occurred mainly in the phylum Proteobacteria independent of high ARG content and contig length. We evaluated the stochasticity of co-localization occurrence using enrichment scores. The most common forms of co-localization involved tetracycline and fluoroquinolone resistance genes, and, on plasmids, co-localization predominantly occurred in the form of class 1 integrons. Antibiotic use caused a short-term increase in mobile ARGs, while non-mobile ARGs showed no significant change. Finally, we found that a high abundance of VGs was associated with low gut microbial maturity and that VGs showed even higher potential for mobility than ARGs.

Conclusions
We found that the phenomenon of co-localization between ARGs and other resistance and VGs was prevalent in the gut at the beginning of life. It reveals the diversity that sustains antibiotic resistance and therefore indirectly emphasizes the need to apply caution in the use of antimicrobial agents in clinical practice, animal husbandry, and daily life to mitigate the escalation of resistance.
Long-term survival rates of tapered self-tapping bone-level implants after immediate placement: a positional effective rationale
Authors: Aung Yoon Thu , Eo Mi Young , Sodnom-Ish Buyanbileg , Kim Myung Joo , Kim Soung Min 
Published: May 2024

Abstract
Background
Immediate implant placement has gained popularity due to its several advantages. However, immediate placement has its challenges, including concerns about primary stability and bone formation around the implant. The aim of the present study is to evaluate the clinical outcomes of tapered, sand-blasted, and acid-etched internal submerged dental implants in various regions of the jaw bones and to provide a positional rationale for immediate implant placement.

Methods
Between 2009 and 2018, a single surgeon at Seoul National University Dental Hospital in Seoul, Korea, immediately inserted 49 dental implants with tapered bone-level design after extraction, in a total of 34 patients. The clinical outcomes were collected and evaluated, focusing on location of implant placement and marginal bone loss (MBL), with consideration of other parameters such as implant diameter and length.

Results
Of 49 immediately installed Luna® (Shinhung Co., Seoul, Korea) dental implants, 23 were placed in the mandible, and 26 were set in the maxilla. The mean age of patients at the time of installation was 65.91 years, ranging from 40 to 86 years. The average follow-up period was 7.43 years, with a range of 5 to 14 years. After a 5-year retrospective evaluation of tapered, sand-blasted, and acid-etched internal submerged dental implants for immediate implant placement, the cumulative survival rate was 93.88%, with 100% survival rate in the mandible and premolar region of both the maxilla and mandible.

Conclusions
After a 5-year evaluation, tapered, sand-blasted, and acid-etched internal submerged dental implants demonstrated good efficacy for immediate placement in various locations within the dental arches, exhibiting effective clinical performance.
Biomechanics of biting in loggerhead shrikes: jaw-closing force, velocity and an argument for power
Authors: Sustaita Diego , Laurin Mason A. 
Published: May 2024

ABSTRACT
Differences in the physical and behavioral attributes of prey are likely to impose disparate demands of force and speed on the jaws of a predator. Because of biomechanical trade-offs between force and speed, this presents an interesting conundrum for predators of diverse prey types. Loggerhead shrikes (Lanius ludovicianus) are medium-sized (∼50 g) passeriform birds that dispatch and feed on a variety of arthropod and vertebrate prey, primarily using their beaks. We used high-speed video of shrikes biting a force transducer in lateral view to obtain corresponding measurements of bite force, upper and lower bill linear and angular displacements, and velocities. Our results show that upper bill depression (about the craniofacial hinge) is more highly correlated with bite force, whereas lower bill elevation is more highly correlated with jaw-closing velocity. These results suggest that the upper and lower jaws might play different roles for generating force and speed (respectively) in these and perhaps other birds as well. We hypothesize that a division of labor between the jaws may allow shrikes to capitalize on elements of force and speed without compromising performance. As expected on theoretical grounds, bite force trades-off against jaw-closing velocity during the act of biting, although peak bite force and jaw-closing velocity across individual shrikes show no clear signs of a force–velocity trade-off. As a result, shrikes appear to bite with jaw-closing velocities and forces that maximize biting power, which may be selectively advantageous for predators of diverse prey that require both jaw-closing force and speed.
Congressional Apportionment: A Multiobjective Optimization Approach
Authors: Shechter Steven M. 
Published: May 2024

Two events, with major implications for U.S. voters, occur after each decennial census. First, congressional “apportionment” takes place, followed by congressional “districting.” Apportionment determines how to allocate the 435 seats in the House of Representatives across the 50 states, whereas districting determines the geographic boundaries assigned to representatives within each state. Although districting and the practice of gerrymandering often receive great attention in the media and courts, the best way to apportion representatives across states has been debated for nearly 250 years. Historical methods (including the current method) each satisfy some desirable optimality criteria that the others are not guaranteed to satisfy. Moreover, none are guaranteed to optimize certain reasonable fairness measures (e.g., minimum range, minimum bias). To our knowledge, we are the first to formulate and analyze a multiobjective optimization approach to apportionment, allowing policymakers to identify Pareto-optimal allocations and quantify their trade-offs between several competing criteria. Some of these models can be formulated and solved as mixed-integer linear programs, whereas others require the solution of mixed-integer, nonconvex, quadratically constrained quadratic programs. We take advantage of recent software advances that allow one to solve these problems with optimality guarantees. Policy implications of our work include Pareto curves from historical censuses and simulations, which suggest opportunities for improvement in some objectives at little sacrifice to others. This paper was accepted by David Simchi-Levi, operations management. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2023.02472 .
CAN WE PREDICT DAIR FAILURE IN PJI? EXTERNAL VALIDATION OF THE KLIC AND CRIME80 SCORES
Authors: Hoffman Tom , Knudsen Joshua , Jesani Satyen , Clark Helen 
Published: May 2024

IntroductionDebridement, antibiotics irrigation and implant retention (DAIR) is a common management strategy for hip and knee prosthetic joint infections (PJI). However, failure rates remain high, which has led to the development of predictive tools to help determine success. These tools include KLIC and CRIME80 for acute-postoperative (AP) and acute haematogenous (AH) PJI respectively. We investigated whether these tools were applicable to a Waikato cohort.MethodWe performed a retrospective cohort study that evaluated patients who underwent DAIR between January 2010 and June 2020 at Waikato Hospital. Pre-operative KLIC and CRIME80 scores were calculated and compared to success of operation. Failure was defined as: (i) need for further surgery, (ii) need for suppressive antibiotics, (iii) death due to the infection. Logistic regression models were used to calculate the area under the curve (AUC).Results117 eligible patients underwent DAIR, 53 in the AP cohort and 64 in the AH cohort. Failure rate at 2 years post-op was 43% in the AP cohort and 59% in the AH cohort. In the AP cohort a KLIC score of <4 had a DAIR failure rate of 28.6%, while those who scored ³4 had a failure rate of 72.2% (p=0.002). In the AH cohort a CRIME80 score of <3 had a DAIR failure rate of 48% while those who scored ³3 had a 100% failure rate (p<0.001).DiscussionThis study represents the first external validation of the KLIC and CRIME80 scores for predicting DAIR failure in an Australasian population. The results indicate that both KLIC and CRIME80 scoring tools are valuable aids for the clinician seeking to determine the optimal management strategy in patients with AP or AH PJI.
IN VIVO ACCURACY OF A NEW ROBOTICALLY ASSISTED SYSTEM FOR TOTAL KNEE ARTHROPLASTY: A PROSPECTIVE COHORT STUDY
Authors: Zaidi F. , Goplen C. M. , Fitz-Gerald C. , Bolam S. M. , Hanlon M. , Munro J. , Monk A. P. 
Published: May 2024

IntroductionRecent technological advancements have led to the introduction of robotic-assisted total knee arthroplasty to improve the accuracy and precision of bony resections and implant position. However, the in vivo accuracy is not widely reported. The primary objective of this study is to determine the accuracy and precision of a cut block positioning robotic arm.MethodSeventy-seven patients underwent total knee arthroplasty with various workflows and alignment targets by three arthroplasty-trained surgeons with previous experience using the ROSA® Knee System. Accuracy and precision were determined by measuring the difference between various workflow time points, including the final pre-operative plan, validated resection angle, and post-operative radiographs. The mean difference between the measurements determined accuracy, and the standard deviation represented precision.ResultsThe accuracy and precision for all angles comparing the final planned resection and validated resection angles was 0.90° ± 0.76°. The proportion within 3° ranged from 97.9% to 100%. The accuracy and precision for all angles comparing the final intra- operative plan and post-operative radiographs was 1.95 ± 1.48°. The proportion of patients within 3° was 93.2%, 95.3%, 96.6%, and 71.4% for the distal femur, proximal tibia, femoral flexion, and tibial slope angles when the final intra-operative plan was compared to post-operative radiographs. No patients had a postoperative complication requiring revision at the final follow-up.ConclusionsThis study demonstrates that the ROSA Knee System has accurate and precise coronal plane resections with few outliers. However, the tibial slope demonstrated decreased accuracy and precision were measured on post-operative short-leg lateral radiographs with this platform.