bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors
Authors: Zang Yi , Su Mingbo , Wang Qingxing , Cheng Xi , Zhang Wenru , Zhao Yao , Chen Tong , Jiang Yingyan , Shen Qiang , Du Juan , Tan Qiuxiang , Wang Peipei , Gao Lixin , Jin Zhenming , Zhang Mengmeng , Li Cong , Zhu Ya , Feng Bo , Tang Bixi , Xie Han , Wang Ming-Wei , Zheng Mingyue , Pan Xiaoyan , Yang Haitao , Xu Yechun , Wu Beili , Zhang Leike , Rao Zihe , Yang Xiuna , Jiang Hualiang , Xiao Gengfu , Zhao Qiang , Li Jia 
Published: September 2022

Abstract
The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (Mpro) and papain like protease (PLpro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851Mpro inhibitors and 205 PLpro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both Mpro and PLpro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of Mpro inhibitors and over 20% of PLpro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 Mpro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Speciation Hypotheses from Phylogeographic Delimitation Yield an Integrative Taxonomy for Seal Salamanders (Desmognathus monticola)
Authors: Pyron R Alexander , O’Connell Kyle A , Duncan Sophie C , Burbrink Frank T , Beamer David A 
Published: September 2022

AbstractSignificant advances have been made in species delimitation and numerous methods can test precisely defined models of speciation, though the synthesis of phylogeography and taxonomy is still sometimes incomplete. Emerging consensus treats distinct genealogical clusters in genome-scale data as strong initial evidence of speciation in most cases, a hypothesis that must therefore be falsified under an explicit evolutionary model. We can now test speciation hypotheses linking trait differentiation to specific mechanisms of divergence with increasingly large data sets. Integrative taxonomy can, therefore, reflect an understanding of how each axis of variation relates to underlying speciation processes, with nomenclature for distinct evolutionary lineages. We illustrate this approach here with Seal Salamanders (Desmognathus monticola) and introduce a new unsupervised machine-learning approach for species delimitation. Plethodontid salamanders are renowned for their morphological conservatism despite extensive phylogeographic divergence. We discover 2 geographic genetic clusters, for which demographic and spatial models of ecology and gene flow provide robust support for ecogeographic speciation despite limited phenotypic divergence. These data are integrated under evolutionary mechanisms (e.g., spatially localized gene flow with reduced migration) and reflected in emergent properties expected under models of reinforcement (e.g., ethological isolation and selection against hybrids). Their genetic divergence is prima facie evidence for species-level distinctiveness, supported by speciation models and divergence along axes such as behavior, geography, and climate that suggest an ecological basis with subsequent reinforcement through prezygotic isolation. As data sets grow more comprehensive, species-delimitation models can be tested, rejected, or corroborated as explicit speciation hypotheses, providing for reciprocal illumination of evolutionary processes and integrative taxonomies. [Desmognathus; integrative taxonomy; machine learning; species delimitation.]
Optimization of depreciation subsidy policy strategies for electric two-wheelers for improving traffic safety
Authors: Li Xintong , Huang Helai , Han Chunyang , Xu Guangming , Lee Jaeyoung , Hu Cheng 
Published: September 2022

Abstract
To improve the traffic safety of electric two-wheelers (ETW), China has promulgated ETW standardization policies. This policy requires local governments to take measures to guide the illegal ETWs out of use. Governments have implemented a depreciation subsidy scheme to encourage users to scrap illegal ETWs early. When designing the subsidy scheme, effectively improving the ETWs' traffic safety at the road network level while saving government expenses is essential for the sustainable implementation of the policy. This study proposes an optimization method for depreciation subsidy design incorporating traffic safety evaluation. Based on the policy scheme, this study formulates a risk assessment model for the ETW traffic network to characterize the effect of the subsidy on improving safety. Then, we use the bi-level programming approach to model the subsidy strategy design problem. The upper-level problem reflects the goal of policymakers to maximize safety improvement and minimize government expenses. The lower-level problem describes the route choices of ETW users. The optimal subsidy design under different safety-expense trade-offs is analysed based on the Nguyen and Dupuis network and a real network extracted from Changsha City in China. The results show that specific subsidy schemes effectively improve road safety without a large government spending. When the market price or service life of ETWs increases, the government spending on the same safety goal increases. The government should comprehensively consider the safety effect of financial expense and the situation of the local ETW market before selecting reasonable subsidy strategies.
Accumulation of copy-back viral genomes during respiratory syncytial virus infection is preceded by diversification of the copy-back viral genome population followed by selection
Authors: Felt Sébastien A , Achouri Emna , Faber Sydney R , López Carolina B 
Published: September 2022

Abstract
RNA viruses generate nonstandard viral genomes during their replication, including viral genomes of the copy-back (cbVGs) type that cannot replicate in the absence of a standard virus. cbVGs play a crucial role in shaping virus infection outcomes due to their ability to interfere with virus replication and induce strong immune responses. However, despite their critical role during infection, the principles that drive the selection and evolution of cbVGs within a virus population are poorly understood. As cbVGs are dependent on the virus replication machinery to be generated and replicated, we hypothesized that host factors that affect virus replication exert selective pressure on cbVGs and drive their evolution within a virus population. To test this hypothesis, we used respiratory syncytial virus (RSV) as a model and took an experimental evolution approach by serially passaging RSV in immune-competent human lung adenocarcinoma A549 control and immune-deficient A549 Signal transducer and activator of transcription 1 (STAT1) KO cells, which allow higher levels of virus replication. As predicted, we observed that virus populations accumulated higher amounts of cbVGs in the more permissive A549 STAT1 KO cells over time; however, unexpectedly, the predominant cbVG species after passages in the two conditions were different. While A549 STAT1 KO cells accumulated relatively short cbVGs, A549 control cells mainly contained cbVGs of much longer predicted size, which have not been described previously. These long cbVGs were predominant at first in both cell lines in vitro and the predominant ones observed in samples from RSV-infected patients. Although sustained high replication levels are associated with cbVG generation and accumulation, our data show that sustained high levels of virus replication are critical for cbVG population diversification, a process that precedes the generation of shorter cbVGs that selectively accumulate over time. Taken together, we show that selection and evolution of cbVGs within a virus population are shaped by how resistant or permissive a host is to RSV.
Volar Plate Interposition Arthroplasty of the Proximal Interphalangeal Joint: A Novel, Modified Malerich’s Technique
Authors: Faccio Marina , Galeano Mariarosaria , Colonna Michele Rosario , Bulli Mattia , Checcucci Giuseppe 
Published: September 2022

Summary:
The choice of prosthetic or autologous reconstruction for proximal interphalangeal (PIP) joint arthroplasty in degenerative osteoarthritis represents a challenge for hand surgeons, especially in consideration of complications and patient’s quality of life. We report the case of a 49-year-old woman who developed diffuse arthritis of the finger joints, especially at the PIP joint of the third right finger. Radiographs showed destruction of the PIP joint, large osteophytes, marked narrowing of joint space, severe sclerosis, and deformation of bone contour. Through a volar approach, we removed the osteophytes, reshaped the joint, and performed an arthroplasty with volar plate interposition. The patient had an improved range of motion at 3 months postoperatively. This case study gives a detailed description and discussion, together with literature revision, of volar plate interposition arthroplasty to treat PIP osteoarthritis, as an alternative to other methods.
Postoperative Outcomes following a Multidisciplinary Approach to HIV-positive Breast Cancer Patients
Authors: Sayyed Adaah A. , Shin Stephanie , Abu El Hawa Areeg A. , Sogunro Olutayo , Del Corral Gabriel A. , Boisvert Marc E. , Song David H. 
Published: September 2022

Background:
Improvements in human immunodeficiency virus (HIV) treatment resulted in drastic increases in the lifespan of HIV-positive individuals, resulting in higher rates of non-AIDS-defining cancers. We describe our postoperative outcomes in HIV+ breast cancer (BC) patients, highlighting our multidisciplinary experience with this high-risk population.

Methods:
A 7-year multi-institutional retrospective review of all HIV+ BC patients who underwent surgical intervention was performed. Patient demographics, therapeutic interventions, and treatment outcomes were collected.

Results:
Twenty-four patients were identified, including one male patient (4.2%). Most patients were African American (83.3%). Mean age was 52.1 + 9.7 years at the time of diagnosis in HIV+ BC patients. Surgical interventions included lumpectomy (n = 16, 66.7%), simple mastectomy (n = 3, 12.5%), and skin-sparing mastectomy (n = 5. 20.8%). All patients were on antiretroviral therapy, and 81.3% had undetectable viral loads at the time of operation. Seventeen patients (70.8%) underwent breast reconstruction, with three (17.7%) undergoing delayed reconstruction. Thirty-day postoperative complications occurred in three patients (17.6%), including flap necrosis (11.8%), infection (11.8%), dehiscence (5.9%), and return to OR (11.8%). Three patients (12.5%) experienced recurrence at a median of 18 months since operation. Mean follow-up was 51.4 + 33.3 months since BC diagnosis.

Conclusions:
While postoperative complication rates in HIV+ patients trended higher (17.6%) compared with the existing data on breast reconstruction patients overall (10.1%), HIV+ patients did not exhibit increased risk of BC recurrence (12.5%) compared with BC patients overall (12-27%). This highlights the importance of a combined multidisciplinary approach involving infectious disease, breast surgery, and plastic and reconstructive surgery to optimize surgical and oncologic outcomes in these high-risk patients.
Microbiology of Musculoskeletal Infections in People Who Inject Drugs at a Rural Tertiary Care Center
Authors: London Abby , Lin Dan , Schade Meredith 
Published: September 2022

Abstract

Background
Complex musculoskeletal (MSK) infections can occur in people who inject drugs (PWID) leading to significant morbidity. The purpose of this study was to update information on the anatomy and microbiology of MSK infections (MSKIs) in PWID, as well as 1-year outcomes at our hospital.

Methods
We identified adult patients admitted to Penn State Health Milton S. Hershey Medical Center from 2008 to 2018 with infection of the MSK system who self-reported injection drug use. The International Classification of Diseases, Ninth and Tenth Revisions, codes for MSKIs and diagnosis codes related to injection drug use were used to identify the cohort. Age, sex, ethnicity, race, date of admission for infection, location of infection, microbial etiology, method of treatment, comorbidities, and outcome at 1-year were recorded.

Results
Eighty-six distinct infections were found in 82 patients. Most patients were White, non-Hispanic, male, 50 years or younger. Hepatitis C and tobacco use disorder were common comorbidities. The axial skeleton was the most common site of infection. Staphylococcus aureus was the most frequent organism isolated followed by Pseudomonas aeruginosa. Spinal infections were primarily managed medically whereas septic joints were treated with surgery and antibiotics.

Conclusions
Infections of the MSK system are increasing in PWID. The axial skeleton is the site most often involved; S. aureus was the most frequently isolated organism with P. aeruginosa the next most common. Treatment may include surgical management, but all received antimicrobials. An unfortunate number had a relapse of infection, were lost to follow-up, or deceased at 1 year.
Measurement of skeletal muscle volume is useful for predicting prognosis in patients with liver cirrhosis
Authors: Matsui Teppei , Nagai Hidenari , Watanabe Gou , Mouri Kunihide , Yoshimine Naoyuki , Amanuma Makoto , Kobayashi Kojirou , Ogino Yu , Mukozu Takanori , Matsukiyo Yasushi , Daidou Yasuko , Wakui Noritaka , Nakano Shigeru , Momiyama Koichi , Matsuda Takahisa , Igarashi Yoshinori 
Published: September 2022

Background
Hepatic venous pressure gradient (HVPG) and the model for end-stage liver disease (MELD) score were previously reported as prognostic factors for outcome in patients with liver cirrhosis (LC), and recently, the presence of sarcopenia was reported to be an indicator of worse prognosis in these patients.

Aim
This retrospective study aimed to clarify the importance of sarcopenia as a prognostic factor in patients with LC.

Material and methods
The MELD-Na score, HVPG, and skeletal muscle index (SMI) were measured in 202 patients between January 2013 and August 2020. We performed linear regression analysis between HVPG and SMI and calculated suitable cutoff values of HVPG for predicting presarcopenia and of HVPG, ΔSMI (i.e. the decrease in SMI per year, for predicting survival). Overall survival rates with the HVPG and ΔSMI cutoff values were compared by Kaplan–Meier estimates and log-rank tests. Prognostic factors for survival were analyzed by Cox regression univariate and multivariate analyses.

Results
In total, 71% (143/202) of patients presented with presarcopenia. Linear regression showed a significantly negative correlation between HVPG and SMI. Survival was significantly worse in the group with presarcopenia than in the group without. Survival was worse also in the group with an HVPG value ≥ 15 and ΔSMI ≥ −2.4. Cox regression multivariate analyses showed that MELD-Na score, HVPG, HVPG ≥ 15, ΔSMI, and ΔSMI ≥ −2.4 were independent prognostic factors.

Conclusion
Skeletal muscle volume, especially ΔSMI, has a prognostic value equivalent to that of the MELD-Na score and HVPG.
Targeting Cellular Senescence for Age-Related Diseases: Path to Clinical Translation
Authors: Wyles Saranya P. , Tchkonia Tamara , Kirkland James L. 
Published: September 2022

Summary:
Beyond the palliative reach of today’s medicines, medical therapies of tomorrow aim to treat the root cause of age-related diseases by targeting fundamental aging mechanisms. Pillars of aging include, among others, genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. The unitary theory of fundamental aging processes posits that by targeting one fundamental aging process, it may be feasible to impact several or all others given its interdependence. Indeed, pathologic accumulation of senescent cells is implicated in chronic diseases and age-associated morbidities, suggesting that senescent cells are a good target for whole-body aging intervention. Preclinical studies using senolytics, agents that selectively eliminate senescent cells, and senomorphics, agents that inhibit production or release of senescence-associated secretory phenotype factors, show promise in several aging and disease preclinical models. Early clinical trials using a senolytic combination (dasatinib and quercetin), and other senolytics including flavonoid, fisetin, and BCL-xL inhibitors, illustrate the potential of senolytics to alleviate age-related dysfunction and diseases including wound healing. Translation into clinical applications requires parallel clinical trials across institutions to validate senotherapeutics as a vanguard for delaying, preventing, or treating age-related disorders and aesthetic aging.
The Role of NAD+ in Regenerative Medicine
Authors: Conlon Nichola J. 
Published: September 2022

Summary:
The understanding of the molecular and cellular basis of aging has grown exponentially over recent years, and it is now accepted within the scientific community that aging is a malleable process; just as it can be accelerated, it can also be slowed and even reversed. This has far-reaching implications for our attitude and approach toward aging, presenting the opportunity to enter a new era of cellular regenerative medicine to not only manage the external signs of aging but also to develop therapies that support the body to repair and restore itself back to a state of internal well-being. A wealth of evidence now demonstrates that a decline in cellular nicotinamide adenine dinucleotide (NAD+) is a feature of aging and may play a role in the process. NAD+ plays a pivotal role in cellular metabolism and is a co-substrate for enzymes that play key roles in pathways that modify aging. Thus, interventions that increase NAD+ may slow aspects of the aging trajectory, and there is great interest in methods for cellular NAD+ restoration. Given these recent advancements in understanding the cellular aging process, it is important that there is an integration between the basic scientists who are investigating the underlying mechanisms of cellular aging and the surgeons and aesthetic practitioners who are providing antiaging therapies. This will allow the effective translation of this vastly complex area of biology into clinical practice so that people can continue to not only stay looking younger for longer but also experience improved health and wellness.
The Precision of Different Types of Plates Fabricated With a Computer-Aided Design and Manufacturing System in Mandibular Reconstruction With Fibular-Free Flaps
Authors: Yodrabum Nutcha , Rudeejaroonrung Krit , Viriya Natthaphat , Chaikangwan Irin , Kongkunnavat Natthapong , Tianrungroj Jirapat , Ongsiriporn Mathee , Piyaman Parkpoom , Puncreobutr Chedtha 
Published: September 2022

Computer-assisted surgery (CAS) has been introduced to mandible reconstruction with fibular-free flap in cutting guide placement. When CAS cooperates with different plate fixations, the results show various degrees of errors by which this study aimed to evaluate. Mock surgeries were conducted in 3D-printed mandibles with 2 types of defects, limited or extensive, reconstructed from 2 ameloblastoma patients. Three types of fixations, miniplate, manually bending reconstruction plate, and patient-specific plate, are tested, each of which was performed 3 times in each type of defect, adding up to 18 surgeries. One with the least errors was selected and applied to patients whose 3D-printed mandibles were derived. Finally, in vivo errors were compared with the mock. In limited defect, average errors show no statistical significance among all types. In extensive defect, patient-specific plate had a significantly lower average condylar error than manually bending reconstruction plate and miniplate (8.09±2.52 mm vs. 25.49±2.72 and 23.13±13.54 mm, respectively). When patient-specific plate was applied in vivo, the errors were not significantly different from the mock. Patient-specific plates that cooperated with CAS showed the least errors. Nevertheless, manually bent reconstruction plates and miniplates could be applied in limited defects with caution.
Nation-wide mammography screening participation in Denmark during the COVID-19 pandemic: An observational study
Authors: Olesen Tina Bech , Jensen Henry , Møller Henrik , Jensen Jens Winther , Andersen Berit , Vejborg Ilse , Njor Sisse H. 
Published: September 2022

AbstractBackgroundIn most of the world, the mammography screening programmes were paused at the start of the pandemic, whilst mammography screening continued in Denmark. We examined the mammography screening participation during the COVID-19 pandemic in Denmark.MethodsThe study population comprised all women aged 50-69 years old invited to participate in mammography screening from 2016-2021 in Denmark based on data from the Danish Quality Database for Mammography Screening in combination with population-based registries. Using a generalised linear model, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) of mammography screening participation within 90, 180 and 365 days since invitation during the pandemic in comparison with the previous years adjusting for age, year and month of invitation.ResultsThe study comprised 1,828,791 invitations among 847,766 women. Before the pandemic, 80.2% of invitations resulted in participation in mammography screening within 90 days, 82.7% within 180 days and 83.1% within 365 days. At the start of the pandemic, the participation in screening within 90 days was reduced to 69.9% for those invited in pre-lockdown and to 76.5% for those invited in 1st lockdown. Extending the length of follow-up time to 365 days only a minor overall reduction was observed (PR=0.94; 95% CI: 0.93-0.95 in pre-lockdown and PR=0.97; 95% CI: 0.96-0.97 in 1st lockdown). A lower participation was; however, seen among immigrants and among women with a low income.ConclusionsThe short-term participation in mammography screening was reduced at the start of the pandemic, whilst only a minor reduction in the overall participation was observed with longer follow-up time indicating that women postponed screening. Some groups of women; nonetheless, had a lower participation indicating that the social inequity in screening participation was exacerbated during the pandemic.