bluuebunny/crossref_metadata_2025 huggingface dataset:
ATLAS: protein flexibility description from atomistic molecular dynamics simulations
Authors: Vander Meersche Yann , Cretin Gabriel , Gheeraert Aria , Gelly Jean-Christophe , Galochkina Tatiana
Published: November 2023

Dynamical behaviour is one of the most crucial protein characteristics. Despite the advances in the field of protein structure resolution and prediction, analysis and prediction of protein dynamic properties remains a major challenge, mostly due to the low accessibility of data and its diversity and heterogeneity. To address this issue, we present ATLAS, a database of standardised all-atom molecular dynamics simulations, accompanied by their analysis in the form of interactive diagrams and trajectory visualisation. ATLAS offers a large-scale view and valuable insights on protein dynamics for a large and representative set of proteins, by combining data obtained through molecular dynamics simulations with information extracted from experimental structures. Users can easily analyse dynamic properties of functional protein regions, such as domain limits (hinge positions) and residues involved in interaction with other biological molecules. Additionally, the database enables exploration of proteins with uncommon dynamic properties conditioned by their environment such as chameleon subsequences and Dual Personality Fragments. The ATLAS database is freely available at https://www.dsimb.inserm.fr/ATLAS.
DRMref: comprehensive reference map of drug resistance mechanisms in human cancer
Authors: Liu Xiaona , Yi Jiahao , Li Tina , Wen Jianguo , Huang Kexin , Liu Jiajia , Wang Grant , Kim Pora , Song Qianqian , Zhou Xiaobo
Published: November 2023

Drug resistance poses a significant challenge in cancer treatment. Despite the initial effectiveness of therapies such as chemotherapy, targeted therapy and immunotherapy, many patients eventually develop resistance. To gain deep insights into the underlying mechanisms, single-cell profiling has been performed to interrogate drug resistance at cell level. Herein, we have built the DRMref database (https://ccsm.uth.edu/DRMref/) to provide comprehensive characterization of drug resistance using single-cell data from drug treatment settings. The current version of DRMref includes 42 single-cell datasets from 30 studies, covering 382 samples, 13 major cancer types, 26 cancer subtypes, 35 treatment regimens and 42 drugs. All datasets in DRMref are browsable and searchable, with detailed annotations provided. Meanwhile, DRMref includes analyses of cellular composition, intratumoral heterogeneity, epithelial–mesenchymal transition, cell–cell interaction and differentially expressed genes in resistant cells. Notably, DRMref investigates the drug resistance mechanisms (e.g. Aberration of Drug’s Therapeutic Target, Drug Inactivation by Structure Modification, etc.) in resistant cells. Additional enrichment analysis of hallmark/KEGG (Kyoto Encyclopedia of Genes and Genomes)/GO (Gene Ontology) pathways, as well as the identification of microRNA, motif and transcription factors involved in resistant cells, is provided in DRMref for user’s exploration. Overall, DRMref serves as a unique single-cell-based resource for studying drug resistance, drug combination therapy and discovering novel drug targets.
iNClusive: a database collecting useful information on non-canonical amino acids and their incorporation into proteins for easier genetic code expansion implementation
Authors: Icking Leon-Samuel , Riedlberger Andreas Martin , Krause Fabian , Widder Jonas , Frederiksen Anne Smedegaard , Stockert Fabian , Spädt Michael , Edel Nikita , Armbruster Daniel , Forlani Giada , Franchini Selene , Kaas Paulina , Kırpat Konak Büşra Merve , Krier Fabrice , Lefebvre Maïwenn , Mazraeh Daniel , Ranniger Jeremy , Gerstenecker Johanna , Gescher Pia , Voigt Karsten , Salavei Pavel , Gensch Nicole , Di Ventura Barbara , Öztürk Mehmet Ali
Published: November 2023

The incorporation of non-canonical amino acids (ncAAs) into proteins is a powerful technique used in various research fields. Genetic code expansion (GCE) is the most common way to achieve this: a specific codon is selected to be decoded by a dedicated tRNA orthogonal to the endogenous ones. In the past 30 years, great progress has been made to obtain novel tRNA synthetases (aaRSs) accepting a variety of ncAAs with distinct physicochemical properties, to develop robust in vitro assays or approaches for codon reassignment. This sparked the use of the technique, leading to the accumulation of publications, from which gathering all relevant information can appear daunting. Here we present iNClusive (https://non-canonical-aas.biologie.uni-freiburg.de/), a manually curated, extensive repository using standardized nomenclature that provides organized information on ncAAs successfully incorporated into target proteins as verified by mass spectrometry. Since we focused on tRNA synthetase-based tRNA loading, we provide the sequence of the tRNA and aaRS used for the incorporation. Derived from more than 687 peer-reviewed publications, it currently contains 2432 entries about 466 ncAAs, 569 protein targets, 500 aaRSs and 144 tRNAs. We foresee iNClusive will encourage more researchers to experiment with ncAA incorporation thus contributing to the further development of this exciting technique.
The Use of Packaging Descriptors in a Rapidly Growing Market for Capsule Cigarettes: Evidence From Mexico
Authors: Tseng Tuo-Yen , Welding Kevin , Saenz-de-Miera Belen , Grilo Graziele , Cohen Joanna E
Published: November 2023

Introduction

The global market for capsule cigarettes has grown rapidly, especially in Latin America. This research examined the sales trends and patterns as well as packaging characteristics of capsule cigarette in Mexico in recent years.

Methods

National data on cigarette sales in Mexico between October 2018 and September 2021 licensed from NielsenIQ were supplemented with cigarette pack pictures and Internet searches to determine whether characterizing flavor, concept flavor, and action descriptors were used. Market share in sales value and volume was calculated by capsule and flavor status, descriptors, price tier, manufacturer, pack size, and cigarette length for the whole time period and for each month. Number of unique brand variants was also examined.

Results

Capsule cigarette sales totaled US$4.29 billion or 30.99 billion sticks during the assessed period, comprising 37.7% of the cigarette market share in sales value or 35.5% in sales volume. Over half of capsule cigarettes sold during this time period had concept flavor descriptors, 17.8% contained characterizing flavor descriptors, and 15.1% contained action descriptors that were suggestive of the interactive aspects of capsules. The monthly market share of capsule cigarette sales volume among all cigarette sales in Mexico increased steadily from 33.3% in October 2018 to 37.3% in September 2021.

Conclusions

The expanding capsule cigarette market in Mexico is concerning, given the product’s associated misconceptions of reduced harm and greater appeal among youth. Findings underline the need for enhanced regulations to address the public health threat posed by capsule cigarettes.

Implications

Capsule cigarettes have a substantial market share in Mexico, with increasing popularity. Descriptors and other product characteristics such as cigarette length might be used to increase the appeal and target particular populations. Policy makers should consider banning capsules and flavors in cigarettes including descriptors or other indication in product presentation that could be perceived as denoting a taste, aroma, or sensation, and making the appearance and design of tobacco products more commensurate with the harm they cause by adopting plain and standardized packaging.
A semiconducting hybrid of RhOx/GaN@InGaN for simultaneous activation of methane and water toward syngas by photocatalysis
Authors: Li Dongke , Wu Zewen , Li Yixin , Fan Xiaoxing , Hasan S M Najib , Arafin Shamsul , Rahman Md Afjalur , Li Jinglin , Wang Zhouzhou , Yu Tianqi , Kong Xianghua , Zhu Lei , Sadaf Sharif Md , Zhou Baowen
Published: November 2023

Prior to the eventual arrival of carbon neutrality, solar-driven syngas production from methane steam reforming presents a promising approach to produce transportation fuels and chemicals. Simultaneous activation of the two reactants, i.e. methane and water, with notable geometric and polar discrepancy is at the crux of this important subject yet greatly challenging. This work explores an exceptional semiconducting hybrid of RhOx/GaN@InGaN nanowires for overcoming this critical challenge to achieve efficient syngas generation from methane steam reforming by photocatalysis. By coordinating density functional theoretical calculations and microscopic characterizations, with in situ spectroscopic measurements, it is found that the multifunctional RhOx/GaN interface is effective for simultaneously activating both CH4 and H2O by stretching the C–H and O–H bonds because of its unique Lewis acid/base attribute. With the aid of energetic charge carriers, the stretched C–H and O–H bonds of reactants are favorably cleaved, resulting in the key intermediates, i.e. *CH3, *OH, and *H, to sit on Rh sites, Rh sites, and N sites, respectively. Syngas is subsequently produced via energetically favored pathway without additional energy inputs except for light. As a result, a benchmarking syngas formation rate of 8.1 mol·gcat−1·h−1 is achieved with varied H2/CO ratios from 2.4 to 0.8 under concentrated light illumination of 6.3 W·cm−2, enabling the achievement of a superior turnover number of 10,493 mol syngas per mol Rh species over 300 min of long-term operation. This work presents a promising strategy for green syngas production from methane steam reforming by utilizing unlimited solar energy.
Gender stereotypes embedded in natural language are stronger in more economically developed and individualistic countries
Authors: Napp Clotilde
Published: November 2023

Gender stereotypes contribute to gender imbalances, and analyzing their variations across countries is important for understanding and mitigating gender inequalities. However, measuring stereotypes is difficult, particularly in a cross-cultural context. Word embeddings are a recent useful tool in natural language processing permitting to measure the collective gender stereotypes embedded in a society. In this work, we used word embedding models pre-trained on large text corpora from more than 70 different countries to examine how gender stereotypes vary across countries. We considered stereotypes associating men with career and women with family as well as those associating men with math or science and women with arts or liberal arts. Relying on two different sources (Wikipedia and Common Crawl), we found that these gender stereotypes are all significantly more pronounced in the text corpora of more economically developed and more individualistic countries. Our analysis suggests that more economically developed countries, while being more gender equal along several dimensions, also have stronger gender stereotypes. Public policy aiming at mitigating gender imbalances in these countries should take this feature into account. Besides, our analysis sheds light on the “gender equality paradox,” i.e. on the fact that gender imbalances in a large number of domains are paradoxically stronger in more developed/gender equal/individualistic countries.
Evaluating the Utilization of Synthetic Oligonucleotides as a Positive Control in the Detection of ToBRFV in Pepper Seeds
Authors: McKenzie Zen , Sturdivant Maxwell , Ueckert Jake , Ong Kevin
Published: November 2023

A constant challenge experienced by plant diagnostic laboratories is having reliable and readily available controls. Often, requests must be made from colleagues to obtain materials for use as controls. This can be problematic if the pathogen is not present in the country and/or is subject to regulations. gBlocks are synthetic oligonucleotides that are widely used in genomic-based applications and studies. We evaluated the use of synthesized gBlocks as a positive control for tomato brown rugose fruit virus (ToBRFV) in a seed extraction PCR (SE-PCR) assay. ToBRFV is a highly virulent Tobamovirus that expresses symptoms of mosaic patterns, browning, and undersized wrinkled fruits in tomatoes, peppers, and other solanaceous plants. Transmission occurs in the seeds and can spread via mechanical contamination of equipment, humans, and other infected plants. Regulations with ToBRFV in the United States makes it difficult to obtain a positive biological control for use in diagnostic clinics. Therefore, we wanted to assess whether this synthetic oligonucleotide could serve as a process control. In our study, pepper ( Capsicum annuum) seeds were “spiked” with synthesized oligonucleotides, which were then used as a point of comparison to biologically positive seeds and negative controls by way of quantifying viral titer. The stability of these synthesized oligonucleotides was evaluated over several temperatures and temporal parameters. Our results suggest that the oligonucleotides are suitable for use in the production of synthetically contaminated seeds that are to be used as a positive control in the validation of the diagnostic process for ToBRFV.
Examining the Effects of Prunus Necrotic Ringspot Virus (PNRSV) and Prune Dwarf Virus (PDV) on Peach (Prunus persica) Pollen Health
Authors: Tayal Mandeep , Ratay Alexandra , Swift Nina , Kaur Satinderpal , Russo Olivia , Kariyat Rupesh , Cieniewicz Elizabeth
Published: November 2023

Pollen health is a key determinant of successful plant reproduction and crop yield. Prunus necrotic ringspot virus (PNRSV) and prune dwarf virus (PDV) are pollen-borne viruses of stone fruits, including peaches, primarily transmitted through vegetative propagation (i.e., grafting) and pollen. Here, we investigated the effects of PNRSV and PDV infection on peach pollen morphology, viability, and germination. Our scanning electron microscopy on pollen morphology, as well as pollen viability and germination assays, showed that PNRSV has cultivar-specific effects on pollen health; compared with pollen from virus-negative trees, PNRSV infection resulted in distorted shape, reduced viability, and germination of pollen grains of peach cultivar Red Top, but no significant effects on viability or germination were detected on cultivar Zee Lady pollen grains. PDV infection affected pollen width and reduced pollen viability but did not affect pollen germination when compared between PDV-positive and PDV-negative pollen grains. We discuss our results in terms of potential evolutionary consequences and implications on virus epidemiology and disease management in orchards. Investigating the effects of viral infection on pollen health will ultimately enhance our understanding of the transmission of pollen-borne viruses.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
“Meiosis arrester” C‐natriuretic peptide directly stimulates oocytemtDNAaccumulation and is implicated in aging‐associated oocytemtDNAloss
Authors: Tang Yawen , Cui Jian , Wang Xiaodong , Yang Qianying , Yue Yuan , Gao Chunxiao , Wang Yue , Wang Wenjing , Zhang Shuai , Tian Jianhui , Xi Guangyin , An Lei
Published: November 2023

C‐natriuretic peptide (CNP) is the central regulator of oocyte meiosis progression, thus coordinating synchronization of oocyte nuclear‐cytoplasmic maturation. However, whether CNP can independently regulate cytoplasmic maturation has been long overlooked. Mitochondrial DNA (mtDNA) accumulation is the hallmark event of cytoplasmic maturation, but the mechanism underlying oocyte mtDNA replication remains largely elusive. Herein, we report that CNP can directly stimulate oocyte mtDNA replication at GV stage, and deficiency of follicular CNP may contribute largely to lower mtDNA copy number in in vitro matured oocytes. The mechanistic study showed that cAMP‐PKA‐CREB1 signaling cascade underlies the regulatory role of CNP in stimulating mtDNA replication and upregulating related genes. Of interest, we also report that CNP‐NPR2 signaling is inhibited in aging follicles, and this inhibition is implicated in lower mtDNA copy number in oocytes from aging females. Together, our study provides the first direct functional link between follicular CNP and oocyte mtDNA replication, and identifies its involvement in aging‐associated mtDNA loss in oocytes. These findings, not only update the current knowledge of the functions of CNP in coordinating oocyte maturation but also present a promising strategy for improving in vitro fertilization outcomes of aging females.
Positive Nurse Mentoring: A Call to Action
Authors: Hlebichuk Jeanne , Salinas Margaret
Published: November 2023

It's time for the profession to embrace this essential role.
Hope Amid Chaos: A Hospital Tent in Post-Earthquake Haiti
Authors: Millam Janine
Published: November 2023

A nurse finds human resilience even in the worst conditions.
Depression, anxiety, and stress in pregnant Black people
Authors: Gennaro Susan , Melnyk Bernadette Mazurek , Szalacha Laura A. , Hoying Jacqueline , Cooper Andrea , Aviles Melanie Milagros , O'Connor Caitlin , Gibeau Anne
Published: November 2023

Background:

Guidelines call for pregnant people to be screened for depression and anxiety. Screening may be particularly important for pregnant Black individuals who are reported to be more likely than non-Hispanic White pregnant people to experience prenatal stress, anxiety, and depressive symptoms. The purpose of this study was to determine if depression, anxiety, and stress co-occur in pregnant Black people and to identify which demographic factors are related to these mental health concerns.

Methods:

A subset analysis of an ongoing randomized controlled trial examined the risk of coexisting mental health conditions in pregnant Black people who screened eligible to participate (that is, they had high levels of depression, anxiety, and/or stress) in two urban clinics using a descriptive correlational design.

Results:

Of the 452 pregnant Black people who were screened for eligibility, 194 (42.9%) had elevated scores on depression, anxiety, and/or stress measures and were enrolled in the larger study. The average scores of the 194 enrolled participants were anxiety, mean (M) = 9.16 (standard deviation [SD] = 4.30); depression, M = 12.80 (SD = 4.27); and stress, M = 21.79 (SD = 4.76). More than one-third (n = 70, 36.1%) experienced two symptoms and 64 (33.0%) reported all three symptoms.

Conclusion:

Pregnant Black individuals experience high levels of comorbid mental health distress including depression, anxiety, and stress. The findings indicate that treatment for mental health concerns needs to be broad-based and effective for all three conditions. Prenatal interventions should aim to address mental health distress through screening and treatment of depression, anxiety, and stress, especially for pregnant Black individuals. This study furthers understanding of the prevalence of prenatal mental health conditions in pregnant Black people.
A Framework for Diversifying Obstetrics and Gynecology Training Programs
Authors: Napoé Gnankang Sarah , Parviainen Kristiina E. L. , Gosman Gabriella G. , Olawaiye Alexander B. , Edwards Robert P.
Published: November 2023

There is an urgent need to diversify the physician workforce in obstetrics and gynecology to serve a diverse patient population and mitigate disparities in care. There is a paucity of data on how to improve recruitment of individuals from underrepresented minoritized groups to the field of obstetrics and gynecology. This article outlines important steps for sharing the department's commitment to diversity, equity, and inclusion; addresses ways to attract a diverse applicant pool; and reviews the importance of and need to perform a holistic review of applicants. This commentary also shares some approaches to support faculty and trainees that may lead to sustained increases in diversity. Using this framework, the authors successfully increased the diversity of their obstetrics and gynecology residency program.
Cardiometabolic outcomes in Kronos Early Estrogen Prevention Study continuation: 14-year follow-up of a hormone therapy trial
Authors: Kantarci Kejal , Tosakulwong Nirubol , Lesnick Timothy G. , Kara Firat , Kendall-Thomas June , Kapoor Ekta , Fields Julie A. , James Taryn T. , Lobo Rogerio A. , Manson JoAnn E. , Pal Lubna , Hammers Dustin B. , Malek-Ahmadi Michael , Cedars Marcelle I. , Naftolin Frederick N. , Santoro Nanette , Miller Virginia M. , Harman Sherman M. , Dowling N. Maritza , Gleason Carey E.
Published: November 2023

Objective

This study aimed to determine long-term cardiometabolic effects of hormone therapies initiated within 3 years of onset of menopause after a 14-year follow-up study of participants of the Kronos Early Estrogen Prevention Study (KEEPS).

Methods

KEEPS was a multisite clinical trial that recruited recently menopausal women with good cardiovascular health for randomization to oral conjugated equine estrogens (Premarin, 0.45 mg/d) or transdermal 17β-estradiol (Climara, 50 μg/d) both with micronized progesterone (Prometrium, 200 mg/d) for 12 d/mo, or placebo pills and patch for 4 years. KEEPS continuation recontacted KEEPS participants 14 years after randomization and 10 years after the completion of the 4-year clinical trial to attend in-person clinic visits.

Results

Participants of KEEPS continuation (n = 299 of the 727 KEEPS participants; 41%) had an average age of 67 years (range, 58-73 y). Measurements of systolic and diastolic blood pressures, waist-to-hip ratio, fasting levels of glucose, insulin, lipid profiles, and homeostasis model assessment of insulin resistance were not different among the treatment groups at either KEEPS baseline or at KEEPS continuation visits, or for change between these two visits. The frequency of self-reported diabetes (P = 0.007) and use of diabetes medications was higher in the placebo than the oral conjugated equine estrogens (P = 0.045) or transdermal 17β-estradiol (P = 0.02) groups, but these differences were not supported by the laboratory measurements of glycemia or insulin resistance.

Conclusions

There was no evidence of cardiovascular and/or metabolic benefits or adverse effects associated with 4 years use of oral or transdermal forms of hormone therapy by recently menopausal women with good cardiovascular health after 10 years.
Utilizing 3D Printing for the Surgical Management of Orbital Floor Fractures
Authors: Mukai Sakurako , Tsuge Takuya , Akaishi Satoshi , Ogawa Rei , Kuwahara Hiroaki
Published: November 2023

We present a technique for treating orbital floor fractures using three-dimensional (3D) printing technology and a preoperative template based on the mirror image of the unaffected orbit. Our patient, a 56-year-old man, experienced persistent diplopia in the upward direction and left enophthalmos after previous open reduction internal fixation surgery. To address these complications, we used a simulation of the ideal orbital floor from computed tomography images and used a 3D printer to create a template. Subsequently, an absorbable plate was molded intraoperatively based on this template. Notably, the plate fit seamlessly into the fracture site without requiring any adjustment, reducing the operation time. Postoperative computed tomography scans confirmed successful reduction, improved visual function, and the absence of complications. Our method offers a precise and efficient approach to reconstructing fractured orbital floors. By leveraging 3D printing technology and preoperative templates, surgeons can enhance postoperative outcomes and minimize patient burden. Further investigations are warranted to assess the long-term effectiveness and cost-effectiveness of this technique. Our findings highlight the potential of this approach to improve treatment strategies for patients with orbital floor fractures.
Dacryolithogenesis or Dacryolithiasis—The Story So Far
Authors: Ali Mohammad Javed , Heichel Jens , Paulsen Friedrich
Published: November 2023

The term dacryoliths refers to the concretions found within the lacrimal system. When the term dacryoliths is unspecified, it usually refers to the noninfectious dacryoliths commonly isolated from the lacrimal sac and the nasolacrimal duct. More often, they are diagnosed incidentally during a dacryocystorhinostomy, and the reported incidence among all dacryocystorhinostomy surgeries is 5.7% to as high as 18%. Dacryolithiasis is a complex process occurring within the lacrimal system, and current evidence suggests a multifactorial etiology. The sequence of events can be summarized broadly into 4 stages: stage of susceptibility, stage of initiation/trigger, stage of development, and stage of maintenance. The triggering event is the breach of the lacrimal sac or nasolacrimal duct epithelium, resulting in microtrauma with blood leakage. The blood clots act as a nidus for subsequent sequential laying of mucopeptides, cellular debris present locally, debris washed from the ocular surface, and extraneous agents in tears. This process is aided by altered rheology and composition of the tear film. After the formation of dacryoliths, extracellular neutrophil traps usually form on the surface, which help to maintain the dacryoliths (which do not dissolve). This review highlights and discusses the possible sequence of events during dacryolithiasis.
Incorporation of protein induced by vitamin K absence or antagonist-II into transplant criteria expands beneficiaries of liver transplantation for hepatocellular carcinoma: A multi-center retrospective cohort study in China
Authors: Wang Kai , Dong Libin , Lu Qian , Yang Zhe , Fan Xiaoli , Gao Fengqiang , Ge Wenwen , Wang Zhoucheng , Zhou Zhisheng , Lu Di , Wei Xuyong , Wei Qiang , Zhuang Li , Qin Lunxiu , Ye Qifa , Yang Jiayin , Dong Jiahong , Zheng Shusen , Xu Xiao
Published: November 2023

Introduction:

In order to maximize the utilization of precious donor liver, precisely determining potential hepatocellular carcinoma (HCC) candidates who will benefit from liver transplantation (LT) is essential. As a crucial diagnostic biomarker for HCC, protein induced by vitamin K absence or antagonist-II (PIVKA-II) has become one of the key indicators for assessing tumor recurrence risk after LT. This study aims to investigate the role of PIVKA-II in recipient selection and prognostic stratification.

Methods:

The clinicopathologic data of HCC patients undergoing LT from 2015 to 2020 in 6 Chinese transplant centers were collected. Univariate and multivariate analyses were performed to determine risk factors for disease-free survival (DFS). Based on these risk factors, survival analysis was made by Kaplan-Meier method and their value in prognostic stratification was assessed.

Results:

A total of 522 eligible HCC patients with pre-LT PIVKA-II records were finally included in this study. Tumor burden>8 cm, AFP>400 ng/mL, histopathologic grade III and PIVKA-II>240 mAU/mL were identified as independent risk factors for DFS. DFS of patients with PIVKA-II≤240 mAU/mL (N=288) were significantly higher than those with PIVKA-II>240 mAU/mL (N=234) (1-, 3- and 5-year DFS: 83.2%, 77.3% and 75.9% vs. 75.1%, 58.5% and 50.5%; P<0.001). Compared with Hangzhou criteria (N=305), incorporating PIVKA-II into Hangzhou criteria (including tumor burden, AFP, histopathologic grade) increased the number of patients with eligibility for LT by 21.6% but achieved comparable DFS and OS.

Conclusions:

Incorporating PIVKA-II into existing LT criteria could increase the number of eligible HCC patients without compromising post-LT outcomes.
Artificial intelligence-aided detection for prostate cancer with multi-modal routine health check-up data: an Asian multi-center study
Authors: Song Zijian , Zhang Wei , Jiang Qingchao , Deng Longxin , Du Le , Mou Weiming , Lai Yancheng , Zhang Wenhui , Yang Yang , Jasmine Lim , Liu Kang , Park Jae Young , Chi-Fai Ng , Aik Ong Teng , Wei Qiang , Li Lei , Wei Xuedong , Chen Ming , Cao Zhixing , Wang Fubo , Chen Rui
Published: November 2023

Background:

The early detection of high-grade prostate cancer (HGPCa) is of great importance. However, the current detection strategies result in a high rate of negative biopsies and high medical costs. In this study, we aimed to establish an Asian Prostate Cancer Artificial intelligence (APCA) score with no extra cost other than routine health check-ups to predict the risk of HGPCa.

Patients and methods:

A total of 7476 patients with routine health checkup data who underwent prostate biopsies from January 2008 to December 2021 in eight referral centers in Asia were screened. After data pre-processing and cleaning, 5037 patients and 117 features were analyzed. Seven AI-based algorithms were tested for feature selection and seven AI-based algorithms were tested for classification, with the best combination applied for model construction. The APAC score was established in the CH cohort and validated in a multi-center cohort and in each validation cohort to evaluate its generalizability in different Asian regions. The performance of the models was evaluated using area under the receiver operating characteristic curve (ROC), calibration plot, and decision curve analyses.

Results:

Eighteen features were involved in the APCA score predicting HGPCa, with some of these markers not previously used in prostate cancer diagnosis. The area under the curve (AUC) was 0.76 (95% CI:0.74-0.78) in the multi-center validation cohort and the increment of AUC (APCA vs. PSA) was 0.16 (95% CI:0.13-0.20). The calibration plots yielded a high degree of coherence and the decision curve analysis yielded a higher net clinical benefit. Applying the APCA score could reduce unnecessary biopsies by 20.2% and 38.4%, at the risk of missing 5.0% and 10.0% of HGPCa cases in the multi-center validation cohort, respectively.

Conclusions:

The APCA score based on routine health checkups could reduce unnecessary prostate biopsies without additional examinations in Asian populations. Further prospective population-based studies are warranted to confirm these results.
Comparison of the postoperative outcome with and without intraoperative leak testing for sleeve gastrectomy: a systematic review and meta-analysis of 469,588 cases
Authors: Ma Longyin , Gao Zhenguo , Luo Heng , Kou Shien , Lei Yu , Jia Victor , Lan Ke , Sankar Subbiah , Hu Jiani , Tian Yunhong
Published: November 2023

Objective:

Postoperative staple line leakage after sleeve gastrectomy is a rare but serious complication. Many surgeons routinely test anastomosis with an intraoperative leak test as part of the sleeve gastrectomy procedure. This meta-analysis aims to determine whether an intraoperative leak test plays a role in reducing the rate of postoperative staple line related complications in patients who underwent sleeve gastrectomy.

Methods:

We searched the PubMed, Web of science, the Cochrane Library and Clinical Trials.gov databases for clinical studies assessing the application of intraoperative leak test (IOLT) in sleeve gastrectomy. The primary endpoint was the development of postoperative staple line leakage. Secondary endpoints included the postoperative bleeding, 30 days mortality rates, and 30 days readmission rates.

Results:

Six studies totaling 469,588 patients met the inclusion criteria. Our review found that the Staple line leakage (SLL) rate was 0.38% (1,221/ 324,264) in the IOLT group and 0.31% (453/ 145,324) in the no intraoperative leak test (NIOLT) group. Postoperative staple line leakage decreased in the NIOLT group compared with the IOLT group (OR=1.27; 95%CI 1.14 to 1.42, P=0.000). Postoperative bleeding was fewer in the IOLT group than that in the NIOLT group (OR 0.79; 95% CI 0.72 to 0.87, P=0.000). There was no significant difference between the IOLT group and the NIOLT group regarding 30 days mortality rates and 30 days readmission rates (P＞0.05).

Conclusion:

IOLT was correlated with an increase in staple line leakage when included as a part of the sleeve gastrectomy procedure. However, IOLT was associated with a lower rate of postoperative bleeding. Thus, IOLT should be considered in sleeve gastrectomy in the situation of suspected postoperative bleeding.
Effect of Video-Assisted Isometric Strengthening Exercise Program on Pain and Muscle Strength Poststabilization of Lower Limb Fracture
Authors: Lee Wan Ling , Ramanathan Shanthi , Danaee Mahmoud , Zaini Noor Hanita , Ramoo Vimala
Published: November 2023

The benefits of isometric strengthening exercises (ISEs) are compromised when patient teaching on ISEs is delayed and/or ineffectively delivered due to healthcare resources constraint, especially when health resources are stretched, as occurred during the COVID-19 pandemic. This study aims to examine the effect of a video-assisted ISE program on pain and muscle strength of patients following surgical stabilization of lower limb fracture. A quasi-experimental study with repeated measures was employed. Primary study outcomes were assessed using the Brief Pain Inventory and Manual Muscle Test. Effects over time were analyzed using generalized estimating equations. In comparison with usual care group (n = 32), the intervention group (n = 33) showed better pain reduction over time (p < .001, effect size [ES] = 0.39–1.77) and muscle strength preservation (p < .05; ES = 0.8–0.9). Patient acceptance of the intervention was favorable. Integration of video clips into patient teaching on ISEs is potentially beneficial in managing pain and muscle strength; it can be easily deployed to aid early ISE initiation.
Blood Management for the Orthopaedic Surgical Patient
Authors: Smyke Norman A. , Sedlak Carol A.
Published: November 2023

Prevention and management of anemia and blood loss in the orthopaedic patient undergoing surgery is a major concern for healthcare providers and patients. Although transfusion technology can be lifesaving, there are risks to blood products that have led to increased awareness of blood management and development of hospital patient blood management programs. Use of patient blood management can be effective in addressing preoperative anemia, a major modifiable risk factor in patients undergoing surgery. In this informational article, evidence-based practice guidelines for perioperative blood management are addressed. A case scenario is introduced focusing on a patient whose religious preference is Jehovah's Witness having “no blood wishes” undergoing elective orthopaedic surgery. Orthopaedic nurses can facilitate optimal patient blood management through multidisciplinary collaboration.
Effect of endometrial thickness on the risk of ectopic pregnancy for frozen embryo transfer
Authors: Huang Li-Juan , Zheng Qu , Wang Xue-Jiao , Zhong Zhao-Hui , Fu Li-Juan , Lv Xing-Yu , Geng Li-Hong , Tang Xiao-Jun , Ding Yu-Bin , Wan Qi
Published: November 2023

Objective:

Few studies have explored the suitability of endometrial thickness (EMT) as a predictor of ectopic pregnancy (EP) in frozen embryo transfer (FET) cycles. Our study aimed to investigate the association between EMT and EP and explore the cutoff value of EMT to predict EP.

Methods:

This retrospective cohort study included women aged 20–45 years undergoing FET between March 2015 and September 2021. The primary outcomes and measured variables were EP and EMT, respectively. The threshold effect of EMT on EP was calculated based on a constructed smooth curve fitting. The patients were divided into two groups based on the threshold for comparison. A subgroup analysis was conducted to examine whether the relationship between EMT and EP remained consistent across the different subgroups. Additionally, a generalized linear model was used to analyze the interactions between the treatment factors and EMT in EP.

Results:

In total, 27,549 FET cycles were included, with 27,086 intrauterine and 463 ectopic pregnancies. The risk of EP in the EMT ≤8.7 mm group was 3.36 times higher than that in the EMT >8.7 mm group (odds ratio [OR]: 3.36, 95% confidence interval [CI]: 2.57–4.05). Subgroup analysis further indicated that a thin EMT was a risk factor for EP, independent of other risks. We also noted that diminished ovarian reserve, tubal factor infertility, transfer of two embryos, or transfer of cleavage-stage embryos may further enhance the risk of EP in patients with thin endometrium.

Conclusions:

Thin endometrium was associated with an increased risk of EP. Patients with EMT less than 8.7 mm need close medical observation and management after embryo transfer. In addition, diminished ovarian reserve, tubal factor infertility, transfer of two embryos, or transfer of cleavage-stage embryos may significantly enhance the effect of a thin endometrium on the risk of EP.
Rapid diagnostic work-up of Streptococcus dysgalactiae endophthalmitis by a novel culture processing system
Authors: Su Erin , Chang Jessica , Ugaban Khay , She Rosemary C.
Published: November 2023

The diagnosis of infective endophthalmitis is supported by microbiological work-up. Rapid work-up is critical to confirm clinical suspicion and appropriate antimicrobial therapy. We report the novel use of an automated liquid culture processing system (FAST system, Qvella, ON, Canada) in a vitreous fluid culture. A 59-year-old patient with post-operative endophthalmitis presented with acute right eye pain and blurred vision. Vitreous fluid collected for microbiology culture was of limited quantity and only inoculated to thioglycolate broth. The broth recovered beta-haemolytic, group G

Streptococcus dysgalactiae

susceptible to penicillin and vancomycin. Experimental application of the FAST system to purify the organism from broth culture yielded the same identification and susceptibility test results but 1 day sooner. Despite prompt treatment with appropriate antibiotics, including vancomycin and ceftazidime, disease progressed rapidly and required enucleation to achieve a stable therapeutic outcome. Use of automated processing of monomicrobial broth cultures has thus far focused on positive blood culture broths, but could potentially include other liquid-based cultures such as for sterile body fluids of critical nature.
Genomic investigation of the emergence of vanD vancomycin resistant Enterococcus faecium
Authors: Baines Sarah L , Guérillot Romain , Ballard Susan , Johnson Paul D R , Stinear Timothy P , Roberts Sally , Howden Benjamin P
Published: November 2023

Vancomycin-resistant Enterococcus (VRE) is an increasingly identified cause of human disease with most infections resulting from the vanA and vanB genotypes; less is known about other clinically relevant genotypes. Here we report a genomic exploration of a vanD VRE faecium (VREfm), which arose de novo during a single infectious episode. The genomes of the vancomycin-susceptible E. faecium (VSEfm) recipient and resulting VREfm were subjected to long-read sequencing and closed, with whole genome alignments and cross-mapping used to identified genomic variation. Three key differences were identified. (i) The VREfm chromosome gained a 142.6kb integrative conjugative element (ICE) harbouring the vanD locus. (ii) The native ligase (ddl) was disrupted by an ISEfm1 insertion. (iii) A large 1.74Mb chromosomal inversion of unknown consequence occurred. Alignment and phylogenetic-based comparisons of the VREfm with a global collection of vanD-harbouring genomes identified strong similarities in the 120-160kb genomic region surrounding vanD, suggestive of a common mobile element and integration site, irrespective of the diverse taxonomic, geographic, and host origins of the isolates. This isolate diversity revealed that this putative ICE (and its source) is globally disseminated and is capable of being acquired by different genera. Although the incidence of vanD VREfm is low, understanding its emergence and potential for spread is crucial for the ongoing efforts to reduce antimicrobial resistance.
DARDN: A deep-learning approach for CTCF binding sequence classification and oncogenic regulatory feature discovery
Authors: Cho Hyun Jae , Wang Zhenjia , Cong Yidan , Bekiranov Stefan , Zhang Aidong , Zang Chongzhi
Published: November 2023

Characterization of gene regulatory mechanisms in cancer is a key task in cancer genomics. CCCTC-binding factor (CTCF), a DNA binding protein, exhibits specific binding patterns in the genome of cancer cells and has a non-canonical function to facilitate oncogenic transcription programs by cooperating with transcription factors bound at flanking distal regions. Identification of DNA sequence features from a broad genomic region that distinguish cancer-specific CTCF binding sites from regular CTCF binding sites can help find oncogenic transcription factors in a cancer type. However, the long DNA sequences without localization information makes it difficult to perform conventional motif analysis. Here we present DNAResDualNet (DARDN), a computational method that utilizes convolutional neural networks (CNNs) for predicting cancer-specific CTCF binding sites from long DNA sequences and employs DeepLIFT, a method for interpretability of deep learning models that explains the model’s output in terms of the contributions of its input features [1], for identifying DNA sequence features associated with cancer-specific CTCF binding. Evaluation on DNA sequences associated with CTCF binding sites in T-cell acute lymphoblastic leukemia (T-ALL) and other cancer types demonstrates DARDN’s ability in classifying DNA sequences surrounding cancer-specific CTCF binding from control constitutive CTCF binding and identifying sequence motifs for transcription factors potentially active in each specific cancer type. We identified potential oncogenic transcription factors in T-ALL, acute myeloid leukemia (AML), breast cancer (BRCA), colorectal cancer (CRC), lung adenocarcinoma (LUAD), and prostate cancer (PRAD). Our work demonstrates the power of advanced machine learning and feature discovery approach in finding biologically meaningful information from complex high-throughput sequencing data.
Structural basis for polyuridine tract recognition by SARS-CoV-2 Nsp15
Authors: Ito Fumiaki , Yang Hanjing , Zhou Z. Hong , Chen Xiaojiang S.
Published: November 2023

SARS-CoV-2 non-structural protein 15 (Nsp15) is critical for productive viral replication and evasion of host immunity. The uridine-specific endoribonuclease activity of Nsp15 mediates the cleavage of the polyuridine [poly(U)] tract of the negative-strand coronavirus genome to minimize the formation of dsRNA that activates the host antiviral interferon signaling. However, the molecular basis for the recognition and cleavage of the poly(U) tract by Nsp15 is incompletely understood. Here, we present cryogenic electron microscopy (cryoEM) structures of SARS-CoV-2 Nsp15 bound to viral replication intermediate dsRNA containing poly(U) tract at 2.7-3.3 Å resolution. The structures reveal one copy of dsRNA binds to the sidewall of an Nsp15 homohexamer, spanning three subunits in two distinct binding states. The target uracil is dislodged from the base-pairing of the dsRNA by amino acid residues W332 and M330 of Nsp15, and the dislodged base is entrapped at the endonuclease active site center. Up to 20 A/U base pairs are anchored on the Nsp15 hexamer, which explains the basis for a substantially shortened poly(U) sequence in the negative strand coronavirus genome compared to the long poly(A) tail in its positive strand. Our results provide mechanistic insights into the unique immune evasion strategy employed by coronavirus Nsp15.
2D versus 3D artificial intelligence-driven segmentations of airway alterations in cystic fibrosis: which one is better?
Authors: Bouzid Imene Hadj , Benlala Ilyes , Dournes Gael
Published: November 2023

Purpose or Learning Objective

Artificial intelligence (AI) with convolutional neural network allows fully automated detection and segmentation of bronchial changes on CT-scans of cystic fibrosis (CF). However, the superiority of two-dimensional (2D) versus three-dimensional (3D) architectures remains to be explored.

Method or Background

CT-scans from fifty CF patients were retrospectively included at two CF reference centers. The nnUnet model was implemented in both 2D and 3D, and trained to segment five structural alterations: bronchiectasis, wall thickening, mucus plugs, bronchiolar impactions and consolidations. A semantic validation was done by using fifty CTs with a five-fold cross validation strategy, by comparing normalized Dice-Sorensen coefficient (DSC) between 2D and 3D architectures, with manual segmentations as Gold Standard.

Results or Findings

The 3D nnUnet was found able to segment the five CF main hallmarks such as bronchiectasis, wall thickening, mucus plugs, bronchiolar impactions and consolidations. Metrics obtained with the 3D architecture were superior for mucus plugs, bronchiolar impactions and consolidations (p<0.001) but not significantly different for bronchiectasis and wall thickening (p>0.05).

Conclusion

AI with the 3D-nnUnet model can perform fully automated segmentation of CF-related structural hallmarks on CT scans, and overcome 2D implementation. Non-invasive, holistic 3D quantifications are allowed for promising next clinical applications.
Mapping Cerebellar Anatomical Heterogeneity in Mental and Neurological Illnesses
Authors: Kim Milin , Leonardsen Esten , Rutherford Saige , Selbæk Geir , Persson Karin , Steen Nils Eiel , Smeland Olav B. , Ueland Torill , Richard Geneviève , Beckmann Christian F. , Marquand Andre F. ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI), Andreassen Ole A. , Westlye Lars T. , Wolfers Thomas , Moberget Torgeir
Published: November 2023

The cerebellum has been linked to motor coordination, cognitive and affective processing, in addition to a wide range of clinical illnesses. To enable robust quantification of individual cerebellar anatomy relative to population norms, we mapped the normative development and aging of the cerebellum across the lifespan using brain scans of > 54k participants. We estimated normative models at voxel-wise spatial precision, enabling integration with cerebellar atlases. Applying the normative models in independent samples revealed substantial heterogeneity within five clinical illnesses: autism spectrum disorder, mild cognitive impairment, Alzheimer’s disease, bipolar disorder, and schizophrenia. Notably, individuals with autism spectrum disorder and mild cognitive impairment exhibited increased numbers of both positive and negative extreme deviations in cerebellar anatomy, while schizophrenia and Alzheimer’s disease predominantly showed negative deviations. Finally, extreme deviations were associated with cognitive scores. Our results provide a voxel-wise mapping of cerebellar anatomy across the human lifespan and clinical illnesses, demonstrating cerebellum’s nuanced role in shaping human neurodiversity across the lifespan and in different clinical illnesses.
Imaging intracellular componentsin situusing super-resolution cryo-correlative light and electron microscopy
Authors: Last Mart G. F. , Voortman Lenard M. , Sharp Thomas H.
Published: November 2023

Super-resolution cryo-correlative light and electron microscopy (SRcryoCLEM) is emerging as a powerful method to enable targetedin situstructural studies of biological samples. By combining the high specificity and localization accuracy of single-molecule localization microscopy (cryoSMLM) with the high resolution of cryo-electron tomography (cryoET), this method enables accurately targeted data acquisition and the observation and identification of biomolecules within their natural cellular context. Despite its potential, the adaptation of SRcryoCLEM has been hindered by the need for specialized equipment and expertise. In this chapter, we outline a workflow for cryoSMLM and cryoET-based SRcryoCLEM, and we demonstrate that, given the right tools, it is possible to incorporate cryoSMLM into an established cryoET workflow. Using Vimentin as an exemplary target of interest, we exemplify all stages of an SRcryoCLEM experiment: performing cryoSMLM, targeting cryoET acquisition based single-molecule localization maps, and correlation of cryoSMLM and cryoET datasets using scNodes, a software package dedicated to SRcryoCLEM. By showing how SRcryoCLEM enables the imaging of specific intracellular components in situ, we hope to facilitate the further adaptation of the technique within the field of cryoEM.