bluuebunny/crossref_metadata_2025 huggingface dataset:
Preventative behaviours and COVID-19 infection in a Canadian cohort of people living with HIV
Authors: Hammond Keely , Lee Terry , Vulesevic Branka , Singer Joel , Needham Judy , Burchell Ann N. , Samji Hasina , Walmsley Sharon , Hull Mark , Jenabian Mohammad-Ali , Routy Jean-Pierre , Margolese Shari , Mandarino Enrico , Anis Aslam H. , Cooper Curtis L. , Costiniuk Cecilia T.
Published: October 2023

Few studies have examined preventative behaviour practices with respect to COVID-19 among people living with HIV (human immunodeficiency virus). Using a cross-sectional survey from a Canadian Institutes of Health Research Canadian HIV Trials Network study (CTN 328) of people living with HIV on vaccine immunogenicity, we examined the relationships between participant characteristics and behavioural practices intended to prevent COVID-19 infection. Participants living in four Canadian urban centers were enrolled between April 2021–January 2022, at which time they responded to a questionnaire on preventative behaviour practices. Questionnaire and clinical data were combined to explore relationships between preventive behaviours and (1) known COVID-19 infection pre-enrolment, (2) multimorbidity, (3) developing symptomatic COVID-19 infection, and (4) developing symptomatic COVID-19 infection during the Omicron wave. Among 375 participants, 49 had COVID-19 infection pre-enrolment and 88 post-enrolment. The proportion of participants reporting always engaging in preventative behaviours included 87% masking, 79% physical distancing, 70% limiting social gatherings, 65% limiting contact with at-risk individuals, 33% self-isolating due to symptoms, and 26% self-quarantining after possible exposure. Participants with known COVID-19 infection pre-enrolment were more likely to self-quarantine after possible exposure although asymptomatic (65.0% vs 23.4%, p < 0.001; Chi-square test). Participants with multiple comorbidities more likely endorsed physical distancing (85.7% vs 75.5%, p = 0.044; Chi-square test), although this was not significant in logistic regression analysis adjusted for age, sex, race, number of household members, number of bedrooms/bathrooms in the household per person, influenza immunization, and working in close physical proximity to others. Overall, participants reported frequent practice of preventative behaviours.
ERRα promotes glycolytic metabolism and targets the NLRP3/caspase-1/GSDMD pathway to regulate pyroptosis in endometrial cancer
Authors: Su Pingping , Mao Xiaodan , Ma Jincheng , Huang Lixiang , Yu Lirui , Tang Shuting , Zhuang Mingzhi , Lu Zhonglei , Osafo Kelvin Stefan , Ren Yuan , Wang Xinrui , Lin Xite , Huang Leyi , Huang Xiaoli , Braicu Elena Ioana , Sehouli Jalid , Sun Pengming
Published: October 2023

Background

Tumor cells can resist chemotherapy-induced pyroptosis through glycolytic reprogramming. Estrogen-related receptor alpha (ERRα) is a central regulator of cellular energy metabolism associated with poor cancer prognosis. Herein, we refine the oncogenic role of ERRα in the pyroptosis pathway and glycolytic metabolism.

Methods

The interaction between ERRα and HIF-1α was verified using co-immunoprecipitation. The transcriptional binding sites of ERRα and NLRP3 were confirmed using dual-luciferase reporter assay and cleavage under targets and tagmentation (CUT&Tag). Flow cytometry, transmission electron microscopy, scanning electron microscopy, cell mito stress test, and extracellular acidification rate analysis were performed to investigate the effects of ERRα on the pyroptosis pathway and glycolytic metabolism. The results of these experiments were further confirmed in endometrial cancer (EC)-derived organoids and nude mice. In addition, the expression of ERRα-related pyroptosis genes was analyzed using The Cancer Genome Atlas and Gene Expression Omnibus database.

Results

Triggered by a hypoxic microenvironment, highly expressed ERRα could bind to the promoter of NLRP3 and inhibit caspase-1/GSDMD signaling, which reduced inflammasome activation and increased pyroptosis resistance, thereby resulting in the resistance of cancer cells to cisplatin. Moreover, ERRα activated glycolytic rate-limiting enzyme to bridge glycolytic metabolism and pyroptosis in EC. This phenomenon was further confirmed in EC-derived organoids and nude mice. CUT & Tag sequencing and The Cancer Genome Atlas database analysis showed that ERRα participated in glycolysis and programmed cell death, which resulted in EC progression.

Conclusions

ERRα inhibits pyroptosis in an NLRP3-dependent manner and induces glycolytic metabolism, resulting in cisplatin resistance in EC cells.
A CRISPR activation screen identifies MUC-21 as critical for resistance to NK and T cell-mediated cytotoxicity
Authors: Lee Dong-hee , Ahn Hyejin , Sim Hye-In , Choi Eunji , Choi Seunghyun , Jo Yunju , Yun Bohwan , Song Hyun Kyu , Oh Soo Jin , Denda-Nagai Kaori , Park Chan-Sik , Irimura Tatsuro , Park Yoon , Jin Hyung-seung
Published: October 2023

Background

Immunotherapy has significantly advanced cancer treatments, but many patients do not respond to it, partly due to immunosuppressive mechanisms used by tumor cells. These cells employ immunosuppressive ligands to evade detection and elimination by the immune system. Therefore, the discovery and characterization of novel immunosuppressive ligands that facilitate immune evasion are crucial for developing more potent anti-cancer therapies.

Methods

We conducted gain-of-function screens using a CRISPRa (CRISPR activation) library that covered the entire human transmembrane sub-genome to identify surface molecules capable of hindering NK-mediated cytotoxicity. The immunosuppressive role and mechanism of MUC21 were validated using NK and T cell mediated cytotoxicity assays. Bioinformatics tools were employed to assess the clinical implications of mucin-21 (MUC21) in cancer cell immunity.

Results

Our genetic screens revealed that MUC21 expression on cancer cell surfaces inhibits both the cytotoxic activity of NK cells and antibody-dependent cellular cytotoxicity, but not affecting complement-dependent cytotoxicity. Additionally, MUC21 expression hinders T cell activation by impeding antigen recognition, thereby diminishing the effectiveness of the immune checkpoint inhibitor, anti-PD-L1. Moreover, MUC21 expression suppress the antitumor function of both CAR-T cells and CAR-NK cells. Mechanistically, MUC21 facilitates immune evasion by creating steric hindrance, preventing interactions between cancer and immune cells. Bioinformatics analysis revealed elevated MUC21 expression in lung cancer, which correlated with reduced infiltration and activation of cytotoxic immune cells. Intriguingly, MUC21 expression was higher in non-small cell lung cancer (NSCLC) tumors that were non-responsive to anti-PD-(L)1 treatment compared to responsive tumors.

Conclusions

These findings indicate that surface MUC21 serves as a potent immunosuppressive ligand, shielding cancer cells from NK and CD8+T cell attacks. This suggests that inhibiting MUC21 could be a promising strategy to improve cancer immunotherapy.
Unnecessity of routine chest tube drainage after patent ductus arteriosus ligation in preterm neonates
Authors: Lee Youngok , Jung Hanna
Published: October 2023

Background

Conventionally, a chest tube drainage is placed following patent ductus arteriosus (PDA) ligation to monitor possible bleeding and drain air or effusion postoperatively. However, the necessity of chest tube drainage after thoracotomy in PDA ligation is controversial. We evaluated the feasibility and safety of omitting chest tube drainage in preterm neonates who underwent PDA ligation via thoracotomy.

Methods

We retrospectively reviewed the medical records of 56 preterm neonates who underwent surgical ligation of PDA via thoracotomy in the neonatal intensive care unit between January 2014 and March 2022.

Results

The median gestational age was 26.9 (interquartile range [IQR]: 25.9–28.8) weeks and the median body weight at birth was 895 (IQR: 795–1190) g. The median age on the day of surgery was 17.0 (IQR: 10.0–22.0) days and the median body weight on the day of surgery was 1100 (IQR: 958–1410) g. The median operative time was 44.5 (IQR: 35.5–54.0) minutes. There were no intraoperative events or procedure-related deaths. On postoperative chest radiographs, no patients had major complications, such as pneumothorax or hemothorax. Nineteen patients (34%) had minor complications of subcutaneous emphysema around the thoracotomy site. No patients required additional chest tube drainage for postoperative bleeding, pleural effusion, or progressive subcutaneous emphysema. No patients had surgical wound infections. There were seven in-hospital mortalities, which were unrelated to the surgery.

Conclusions

Omitting chest tube drainage is feasible and safe for the postoperative management of preterm neonates undergoing PDA ligation via thoracotomy.
Culex modestus: the overlooked mosquito vector
Authors: Soto Alina , Delang Leen
Published: October 2023

Culex (Barraudius) modestus (Ficalbi 1889) are found in temperate regions across Europe, Asia, and Northern Africa. These mosquitoes thrive during the summer and prefer to breed in permanent vegetative habitats such as rice paddies and marshes. Culex modestus feed on a wide range of bird species but are highly attracted to humans, which makes them a potential ‘bridge’ vector for enzootic pathogens. There is compelling evidence that Culex modestus is an efficient vector for West Nile virus, potentially capable of causing epidemics in humans and other mammals. This species is also a likely vector for Usutu virus, avian malaria (Plasmodium spp.), and parasitic heartworms (Dirofilaria spp.). Culex modestus can be morphologically identified at the larval and adult stages, and a distinctive phenotype of this species is their ability to overwinter. Despite the widespread establishment of this mosquito species and their role as vectors for human pathogens, we lack sufficient knowledge on this species to implement and evaluate targeted vector control measures. Since Culex modestus can be considered a potential public health threat, there is a need for a better understanding of this mosquito species.

Graphical Abstract
Platelet-derived circulating soluble P-selectin is sufficient to induce hematopoietic stem cell mobilization
Authors: Wang Tso-Fu , Liou Yu-Shan , Yang Shang-Hsien , Lin Guan-Ling , Chiang Ya-Wen , Lien Te-Sheng , Li Chi-Cheng , Wang Jen-Hung , Chang Hsin-Hou , Sun Der-Shan
Published: October 2023

Background

Granulocyte colony-stimulating factor (G-CSF)-mediated mobilization of hematopoietic stem cells (HSCs) is a well-established method to prepare HSCs for transplantation nowadays. A sufficient number of HSCs is critical for successful HSC transplantation. However, approximately 2–6% of healthy stem cell donors are G-CSF-poor mobilizers for unknown reasons; thus increasing the uncertainties of HSC transplantation. The mechanism underlining G-CSF-mediated HSC mobilization remains elusive, so detailed mechanisms and an enhanced HSC mobilization strategy are urgently needed. Evidence suggests that P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) are one of the cell–cell adhesion ligand–receptor pairs for HSCs to keep contacting bone marrow (BM) stromal cells before being mobilized into circulation. This study hypothesized that blockage of PSGL-1 and P-selectin may disrupt HSC-stromal cell interaction and facilitate HSC mobilization.

Methods

The plasma levels of soluble P-selectin (sP-sel) before and after G-CSF administration in humans and male C57BL/6J mice were analyzed using enzyme-linked immunosorbent assay. Male mice with P-selectin deficiency (Selp−/−) were further employed to investigate whether P-selectin is essential for G-CSF-induced HSC mobilization and determine which cell lineage is sP-sel derived from. Finally, wild-type mice were injected with either G-CSF or recombinant sP-sel to investigate whether sP-sel alone is sufficient for inducing HSC mobilization and whether it accomplishes this by binding to HSCs and disrupting their interaction with stromal cells in the BM.

Results

A significant increase in plasma sP-sel levels was observed in humans and mice following G-CSF administration. Treatments of G-CSF induced a decrease in the level of HSC mobilization in Selp−/− mice compared with the wild-type (Selp+/+) controls. Additionally, the transfer of platelets derived from wild-type mice can ameliorate the defected HSC mobilization in the Selp−/− recipients. G-CSF induces the release of sP-sel from platelets, which is sufficient to mobilize BM HSCs into the circulation of mice by disrupting the PSGL-1 and P-selectin interaction between HSCs and stromal cells. These results collectively suggested that P-selectin is a critical factor for G-CSF-induced HSC mobilization.

Conclusions

sP-sel was identified as a novel endogenous HSC-mobilizing agent. sP-sel injections achieved a relatively faster and more convenient regimen to mobilize HSCs in mice than G-CSF. These findings may serve as a reference for developing and optimizing human HSC mobilization in the future.
Quality management overview for the production of a tissue-engineered human skin substitute in Malaysia
Authors: Seet Wan Tai , Mat Afandi Mohd Asyraf , Ishak Mohamad Fikeri , Hassan Muhammad Najib Fathi , Ahmat Nazeha , Ng Min Hwei , Maarof Manira
Published: October 2023

Treatments for skin injuries have recently advanced tremendously. Such treatments include allogeneic and xenogeneic transplants and skin substitutes such as tissue-engineered skin, cultured cells, and stem cells. The aim of this paper is to discuss the general overview of the quality assurance and quality control implemented in the manufacturing of cell and tissue product, with emphasis on our experience in the manufacturing of MyDerm®, an autologous bilayered human skin substitute. Manufacturing MyDerm®requires multiple high-risk open manipulation steps, such as tissue processing, cell culture expansion, and skin construct formation. To ensure the safety and efficacy of this product, the good manufacturing practice (GMP) facility should establish a well-designed quality assurance and quality control (QA/QC) programme. Standard operating procedures (SOP) should be implemented to ensure that the manufacturing process is consistent and performed in a controlled manner. All starting materials, including tissue samples, culture media, reagents, and consumables must be verified and tested to confirm their safety, potency, and sterility. The final products should also undergo a QC testing series to guarantee product safety, efficacy, and overall quality. The aseptic techniques of cleanroom operators and the environmental conditions of the facility are also important, as they directly influence the manufacturing of good-quality products. Hence, personnel training and environmental monitoring are necessary to maintain GMP compliance. Furthermore, risk management implementation is another important aspect of QA/QC, as it is used to identify and determine the risk level and to perform risk assessments when necessary. Moreover, procedures for non-conformance reporting should be established to identify, investigate, and correct deviations that occur during manufacturing. This paper provides insight and an overview of the QA/QC aspect during MyDerm®manufacturing in a GMP-compliant facility in the Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia.
Experimental transmission of ovine atypical scrapie to cattle
Authors: Konold Timm , Spiropoulos John , Hills Janet , Abdul Hasina , Cawthraw Saira , Phelan Laura , McKenna Amy , Read Lauren , Canoyra Sara , Marín-Moreno Alba , Torres Juan María
Published: October 2023

Classical bovine spongiform encephalopathy (BSE) in cattle was caused by the recycling and feeding of meat and bone meal contaminated with a transmissible spongiform encephalopathy (TSE) agent but its origin remains unknown. This study aimed to determine whether atypical scrapie could cause disease in cattle and to compare it with other known TSEs in cattle. Two groups of calves (five and two) were intracerebrally inoculated with atypical scrapie brain homogenate from two sheep with atypical scrapie. Controls were five calves intracerebrally inoculated with saline solution and one non-inoculated animal. Cattle were clinically monitored until clinical end-stage or at least 96 months post-inoculation (mpi). After euthanasia, tissues were collected for TSE diagnosis and potential transgenic mouse bioassay. One animal was culled with BSE-like clinical signs at 48 mpi. The other cattle either developed intercurrent diseases leading to cull or remained clinical unremarkable at study endpoint, including control cattle. None of the animals tested positive for TSEs by Western immunoblot and immunohistochemistry. Bioassay of brain samples from the clinical suspect in Ov-Tg338 and Bov-Tg110 mice was also negative. By contrast, protein misfolding cyclic amplification detected prions in the examined brains from atypical scrapie-challenged cattle, which had a classical BSE-like phenotype. This study demonstrates for the first time that a TSE agent with BSE-like properties can be amplified in cattle inoculated with atypical scrapie brain homogenate.
The effect of spinal versus general anaesthesia on perioperative muscle weakness in patients having bilateral total hip arthroplasty: a single center randomized clinical trial
Authors: Van Boxstael Sam , Peene Laurens , Dylst Dimitri , Penders Joris , Hadzic Admir , Meex Ingrid , Corten Kristoff , Mesotten Dieter , Thiessen Steven
Published: October 2023

Background

Perioperative neuro-endocrine stress response may contribute to acquired muscle weakness. Regional anaesthesia has been reported to improve the outcome of patients having total hip arthroplasty. In this study, it was hypothesized that spinal anaesthesia (SA) decreases the perioperative neuro-endocrine stress response and perioperatively acquired muscle weakness (PAMW), as compared to general anaesthesia (GA).

Methods

Fifty subjects undergoing bilateral total hip arthroplasty (THA) were randomly allocated to receive a standardized SA (n = 25) or GA (n = 25). Handgrip strength was assessed preoperatively, on the first postoperative day (primary endpoint) and on day 7 and 28. Respiratory muscle strength was measured by maximal inspiratory pressure (MIP). Stress response was assessed by measuring levels of Adrenocorticotropic hormone (ACTH), cortisol and interleukin-6 (IL-6).

Results

Handgrip strength postoperatively (day 1) decreased by 5.4 ± 15.9% in the SA group, versus 15.2 ± 11.7% in the GA group (p = 0.02). The handgrip strength returned to baseline at day 7 and did not differ between groups at day 28. MIP increased postoperatively in patients randomized to SA by 11.7 ± 48.3%, whereas it decreased in GA by 12.2 ± 19.9% (p = 0.04). On day 7, MIP increased in both groups, but more in the SA (49.0 ± 47.8%) than in the GA group (14.2 ± 32.1%) (p = 0.006). Postoperatively, the levels of ACTH, cortisol and IL-6 increased in the GA, but not in the SA group (p < 0.004).

Conclusion

In patients having bilateral THA, SA preserved the postoperative respiratory and peripheral muscle strength and attenuated the neuro-endocrine and inflammatory responses.

Trial registration: clinicaltrials.gov NCT03600454.
Circulating Tumor DNA from Ascites as an alternative to tumor sampling for genomic profiling in ovarian cancer patients
Authors: Kfoury Maria , Hazzaz Reda El , Sanson Claire , Durand Felix Blanc , Michels Judith , Blameble Emeline Colomba , Tang Roseline , Le Formal Audrey , Lecerf Elodie , Gouy Sebastien , Maulard Amandine , Pautier Patricia , Rouleau Etienne , Leary Alexandra
Published: October 2023

Genomic testing is crucial for the management of ovarian cancer. DNA from biopsies at diagnostic laparoscopies or interval debulking surgery after neoadjuvant chemotherapy, has a high failure rate. At relapse, biopsies may not be feasible. The aim of our study was to evaluate the feasibility and usefulness of measuring genomic instability score (GIS) on cell-free DNA (cfDNA) from ascites.

Patients enrolled in a prospective study (NCT03010124) consented to analysis of biological samples. CfDNA was extracted from 1 to 4 ml of double-centrifuged fresh ascites. Targeted Next-generation sequencing (NGS) including TP53 mutation (TP53m) was performed on cfDNA to confirm the presence of tumor cfDNA. Single Nucleotide Polymorphism Array estimating somatic copy number alterations (SCNA) was performed to calculate GIS for Homologous-Recombination deficiency (HRD).

Twenty nine ascites were collected from 20 patients with suspected or confirmed OC. 93% (27/29) samples had detectable cfDNA (median 1120 ng [24-5732]) even when obtained during chemotherapy. A deleterious mutation was identified in 100%, with high allelic frequencies (median 60% [3.3–87%]), confirming that cfDNA was tumoral. SCNA analyses on 17 patients showed 11 high GIS, and 6 low GIS. 4 patients with confirmed BRCA mutation had a high GIS on ascites. When available from the same patient, SCNA profiles on ascites and tumor were superimposable.

Ascites is frequent at diagnosis and relapse and yields large amounts of tumoral cfDNA. SCNA analysis on ascitic cfDNA is feasible and can detect the same HRD scar as tumor testing. Ascites could provide an alternative to tumor sampling for HRD and BRCA testing.
Exploring the potential of using ChatGPT in physics education
Authors: Liang Yicong , Zou Di , Xie Haoran , Wang Fu Lee
Published: October 2023

The pretrained large language models have been widely tested for their performance on some challenging tasks including arithmetic, commonsense, and symbolic reasoning. Recently how to combine LLMs with prompting techniques has attracted lots of researchers to propose their models to automatically solve math word problems. However, most research works focus on solving math problems at the elementary school level and few works aim to solve problems in science disciplines, e.g., Physics. In this exploratory study, we discussed the potential pedagogical benefits of using ChatGPT in physics and demonstrated how to prompt ChatGPT in solving physics problems. The results suggest that ChatGPT is able to solve some physics calculation problems, explain solutions, and generate new exercises at a human level.
Clockwise rotation of SW Japan and timing of Izanagi–Pacific ridge subduction revealed by arc migration
Authors: Yamaoka Ken , Wallis Simon R.
Published: October 2023

Igneous rocks associated with the Cretaceous to Paleogene volcanic arc in SW Japan show ages that young from west to east in a direction parallel to the Median Tectonic Line suggesting corresponding translation of a heat source traditionally interpreted in terms of oblique subduction of a spreading ridge. However, recent oceanic plate reconstructions suggest ridge subduction may be younger than the main arc activity. Age compilations of 1227 points of felsic to intermediate Cretaceous and Cenozoic igneous rocks from the Japan arc show arc magmatism that can be separated into an early active period 130–60 Ma (stage 1), a subsequent period of quiescence 60–46 Ma (stage 2), which is followed by a resumption of igneous activity from 46 Ma onward (stage 3). In southwest Japan, the orientations of the magmatic arcs of stages 1 and 3 show and angular discordance of about 20°. The lack of active arc magmatism and the occurrence patterns of adakitic and high-Mg andesitic magmas indicate that ridge subduction occurred during stage 2. The arc age distribution pattern of stage 1 is explained by the slab shallowing related to a younging of the subducting slab as the ridge approaches. Furthermore, the obliquity of the arcs formed at stages 1 and 3 is explained by a 20° clockwise rotation of the inner zone of southwest Japan during the ridge-subduction phase. Oceanic plate reconstructions show counterclockwise rotation in the subduction direction after the ridge subduction phase, and coupling of the subducting oceanic plate with the upper plate would support microplate rotation in the inner zone. The new proposed tectonic reconstructions provide a framework to related Paleogene subduction of an active spreading ridge along the east Asia margin not only to the distribution of granitic bodies but also to rift-related basin formation on the eastern margin of the Eurasian continent and to rotation of crustal blocks indicated by paleomagnetic data of Cretaceous terranes.
Herpes zoster vaccine awareness and acceptance among adults in Saudi Arabia: a survey-based cross-sectional study
Authors: AlMuammar Sarah , Albogmi Afaf , Alzahrani Manar , Alsharef Fai , Aljohani Raghad , Aljilani Teif
Published: October 2023

Background

Herpes zoster (shingles) is caused by reactivation of the varicella-zoster virus. Despite the recommended herpes zoster vaccine for individuals aged ≥ 50 years, its uptake remains low in Saudi Arabia.

Methods

This cross-sectional study assessed knowledge and awareness of herpes zoster and its vaccine in individuals aged ≥ 50 years in Saudi Arabia. Data were collected through an online survey distributed via social media.

Results

Among 402 participants, 57.2% had heard of the shingles vaccine, but only 7.7% received it. However, 53.2% expressed willingness to be vaccinated. Multivariable analysis revealed that those aged 56–60 were 1.8 times more likely to accept the vaccine than those aged 50–55 years (p = 0.03). Men were 1.9 times more likely to accept the vaccine than women (p = 0.01). Additionally, participants with a primary education were 16.1 times more likely to accept the vaccine than those with a higher education (p = 0.01).

Conclusion

This study highlights the need for increased awareness and education among healthcare providers and the public in Saudi Arabia regarding shingles and its vaccine. The low vaccine uptake calls for effective strategies, such as awareness campaigns and provider reminders. Primary education and vaccine hesitancy influence willingness to be vaccinated.
Genetic characteristics of spouse selection based on short tandem repeats in DNA and lunula count on fingertip
Authors: Xia Qi , Anwar Ullah , Weijian Yu , Yingshuai Wang , Hui Liu
Published: October 2023

Objective

The aim of this study was to assess the correlation of spouse selection withshort tandem repeats (STRs) in DNA and with the number of fingertip lunulae to investigate the role of heredity in spouse selection.

Methods

We randomly selected a total of 286 couples (husband and wife) as a couple group while 200 paired subjects (a man randomly matched with a woman as a pair of subjects) were selected as a non-spouse group for DNA typing, and to investigate lunulae in spouse selection, a total of 554 couples were selected as a couple group and 500 pairs of subjects were selected as a control group.

Results

A significant difference of STR matching number (a large value implies a higher genetic similarity) between spouse group and non-spouse group were observed (12.3 ± 2.7 vs. 11.8 ± 2.6; p < 0.05). A significant difference of the lunula matching number (difference of lunula counts between a paired subjects, a lower value implies a higher genetic similarity) between two groups were also observed for the lunula counts (1.55 ± 1.88 vs. 3.53 ± 2.40; p < 0.01).

Conclusion

Significant and unprecedented relationships were found between the couples and polymorphic STRs, and between spouse selection and lunula counts. Polymorphic STRs and fingertip lunulae counts provide an initial insight into the potentially important contributions that genetic characteristics may play a key role in spouse selection.
Examining post-error performance in a complex multitasking environment
Authors: Lewis Christina M. , Gutzwiller Robert S.
Published: October 2023

Previous work on indices of error-monitoring strongly supports that errors are distracting and can deplete attentional resources. In this study, we use an ecologically valid multitasking paradigm to test post-error behavior. It was predicted that after failing an initial task, a subject re-presented with that task in conflict with another competing simultaneous task, would more likely miss their response opportunity for the competing task and stay ‘tunneled’ on the initially errored task. Additionally, we predicted that an error’s effect on attention would dissipate after several seconds, making error cascades less likely when subsequent conflict tasks are delayed. A multi-attribute task battery was used to present tasks and collect measures of both post-error and post-correct performance. Results supported both predictions: post-error accuracy on the competing task was lower compared to post-correct accuracy, and error-proportions were higher at shorter delays, dissipating over time. An exploratory analysis also demonstrated that following errors (as opposed to post-correct trials), participants clicked more on the task panel of the initial error regardless of delay; this continued task-engagement provides preliminary support for errors leading to a cognitive tunneling effect.
Chemosensitivity to doxorubicin in primary cells derived from tumor of FVB/N-Trp53tm1Hw1 with TALEN-mediated Trp53 mutant gene
Authors: Yun Woobin , Kim Ji Eun , Jin You Jeong , Roh Yu Jeong , Song Hee Jin , Seol Ayun , Kim Tae Ryeol , Min Kyeong Seon , Park Eun Seo , Park Gi Ho , Kang Hyun Gu , Choi Yeon Shik , Hwang Dae Youn
Published: October 2023

Background

To evaluate the chemosensitivity to doxorubicin (DOX) in two primary cells derived from a tumor of FVB/N-Trp53tm1Hw1 knockout (KO) mice with TALEN-mediated Trp53 mutant gene, we evaluated the cell survivability, cell cycle distribution, apoptotic cell numbers and apoptotic protein expression in solid tumor cells and ascetic tumor cells treated with DOX.

Results

The primary tumor cells showed a significant (P < 0.05) defect for UV-induced upregulation of the Trp53 protein, and consisted of different ratios of leukocytes, fibroblasts, epithelial cells and mesenchymal cells. The IC50 level to DOX was lower in both primary cells (IC50 = 0.12 μM and 0.20 μM) as compared to the CT26 cells (IC50 = 0.32 μM), although the solid tumor was more sensitive. Also, the number of cells arrested at the G0/G1 stage was significantly decreased (24.7–23.1% in primary tumor cells treated with DOX, P < 0.05) while arrest at the G2 stage was enhanced to 296.8–254.3% in DOX-treated primary tumor cells compared with DOX-treated CT26 cells. Furthermore, apoptotic cells of early and late stage were greatly increased in the two primary cell-lines treated with DOX when compared to same conditions for CT26 cells. However, the Bax/Bcl-2 expression level was maintained constant in the primary tumor and CT26 cells.

Conclusions

To the best of our knowledge, these results are the first to successfully detect an alteration in chemosensitivity to DOX in solid tumor cells and ascetic tumor cells derived from tumor of FVB/N-Trp53tm1Hw1 mice TALEN-mediated Trp53 mutant gene.
Board characteristics and the likelihood of financial statements fraud: empirical evidence from an emerging market
Authors: Ebaid Ibrahim El-Sayed
Published: October 2023

This study examines the relationship between board characteristics and the likelihood of fraud in financial statements in the Saudi stock exchange as one of the emerging markets. Financial statements of 67 companies listed on the Saudi Stock Exchange have been collected over six years from 2014 to 2019. The modified Beneish M-score model (Beneish in Financ Anal J 55(5):24–36, 1999) has been used to measure fraudulent financial statements. Panel data techniques have been used to examine the relationship between financial statement fraud and four characteristics of the board: independence, size, meetings frequency, and gender diversity. The findings indicate that the likelihood of fraud in financial statements is negatively and significantly related to board independence and it is positively and significantly related to the board size. The results also indicate that the representation of women on the board and the frequency of meetings have no significant relationship with the likelihood of fraud in the financial statements. The results of this study provide insight into the importance of corporate governance mechanisms, including the board of directors, in preventing corporate managers from engaging in fraudulent financial reporting activities. In emerging markets such as the Saudi Stock Exchange, financial statements are the main and almost the only source of information about the company. Therefore, examining the factors that reduce financial statement fraud in these markets is important.
Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Rearranged or Translocated Non–Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04)
Authors: Park Sehhoon , Kim Tae Min , Han Ji-Youn , Lee Gyeong-Won , Shim Byoung Yong , Lee Yun-Gyoo , Kim Sang-We , Kim Il Hwan , Lee Suee , Kim Yu Jung , Park Ji Hyun , Park Sang-Gon , Lee Ki Hyeong , Kang Eun Joo , Kim Ju Won , Shin Seong-Hoon , Ock Chan-Young , Nam Byung-Ho , Lee Jaebong , Jung Hyun-Ae , Sun Jong-Mu , Lee Se-Hoon , Ahn Jin Seok , Ahn Myung-Ju
Published: October 2023

PURPOSE

In the treatment of non–small-cell lung cancer (NSCLC) with a driver mutation, the role of anti–PD-(L)1 antibody after tyrosine kinase inhibitor (TKI) remains unclear. This randomized, open-label, multicenter, phase III study evaluates the efficacy of atezolizumab plus bevacizumab, paclitaxel, and carboplatin (ABCP ) in EGFR- or ALK-rearranged or translocated NSCLC upon progression on TKI therapy.

MATERIALS AND METHODS

We compared the clinical efficacy of ABCP followed by maintenance therapy with atezolizumab plus bevacizumab with pemetrexed plus carboplatin or cisplatin (PC) followed by pemetrexed maintenance. The primary end point was progression-free survival (PFS).

RESULTS

A total of 228 patients with activating EGFR mutation (n = 215) or ALK translocation (n = 13) were enrolled from 16 sites in the Republic of Korea and randomly assigned at 2:1 ratio to either ABCP (n = 154) or PC arm (n = 74). The median follow-up duration was 26.1 months (95% CI, 24.7 to 28.2). Objective response rates (69.5% v 41.9%, P < .001) and median PFS (8.48 v 5.62 months, hazard ratio [HR], 0.62 [95% CI, 0.45 to 0.86]; P = .004) were significantly better in the ABCP than PC arm. PFS benefit increased as PD-L1 expression increased, with an HR of 0.47, 0.41, and 0.24 for PD-L1 ≥1%, ≥10%, and ≥50%, respectively. Overall survival was similar between ABCP and PC arm (20.63 v 20.27 months, HR, 1.01 [95% CI, 0.69 to 1.46]; P = .975). The safety profile of the ABCP arm was comparable with that previously reported, with no additional safety signals, but higher rates of treatment-related adverse events were observed compared with the PC arm.

CONCLUSION

To our knowledge, this study is the first randomized phase III study to demonstrate the clinical benefit of anti–PD-L1 antibody in combination with bevacizumab and chemotherapy in patients with EGFR- or ALK-rearranged or translocated NSCLC who have progressed on relevant targeted therapy.
Machine learning in physics: A short guide
Authors: Rodrigues Francisco A.
Published: October 2023

Machine learning is a rapidly growing field with the potential to revolutionize many areas of science, including physics. This review provides a brief overview of machine learning in physics, covering the main concepts of supervised, unsupervised, and reinforcement learning, as well as more specialized topics such as causal inference, symbolic regression, and deep learning. We present some of the principal applications of machine learning in physics and discuss the associated challenges and perspectives.
Incidence and Determinants of Spontaneous Normalization of Subclinical Hypothyroidism in Older Adults
Authors: van der Spoel Evie , van Vliet Nicolien A , Poortvliet Rosalinde K E , Du Puy Robert S , den Elzen Wendy P J , Quinn Terence J , Stott David J , Sattar Naveed , Kearney Patricia M , Blum Manuel R , Alwan Heba , Rodondi Nicolas , Collet Tinh-Hai , Westendorp Rudi G J , Ballieux Bart E , Jukema J Wouter , Dekkers Olaf M , Gussekloo Jacobijn , Mooijaart Simon P , van Heemst Diana
Published: October 2023

Context

With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown.

Objective

To investigate incidence and determinants of spontaneous normalization of TSH levels in older adults with subclinical hypothyroidism.

Design

Pooled data were used from the (1) pretrial population and (2) in-trial placebo group from 2 randomized, double-blind, placebo-controlled trials (Thyroid Hormone Replacement for Untreated Older Adults With Subclinical Hypothyroidism Trial and Institute for Evidence-Based Medicine in Old Age thyroid 80-plus thyroid trial).

Setting

Community-dwelling 65+ adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom.

Participants

The pretrial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free T4 within the laboratory-specific reference range. Individuals with persistent subclinical hypothyroidism, defined as ≥2 elevated TSH measurements ≥3 months apart, were randomized to levothyroxine/placebo, of which the in-trial placebo group (N = 361) was included.

Main Outcome Measures

Incidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization.

Results

In the pretrial phase, TSH levels normalized in 60.8% of participants in a median follow-up of 1 year. In the in-trial phase, levels normalized in 39.9% of participants after 1 year of follow-up. Younger age, female sex, lower initial TSH level, higher initial free T4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization.

Conclusion

Because TSH levels spontaneously normalized in a large proportion of older adults with subclinical hypothyroidism (also after confirmation by repeat measurement), a third measurement may be recommended before considering treatment.

Trial registration

ClinicalTrials.gov, NCT01660126 and Netherlands Trial Register, NTR3851.
High Lipoprotein(a) May Explain One-Quarter of Clinical Familial Hypercholesterolemia Diagnoses in Danish Lipid Clinics
Authors: Hedegaard Berit Storgaard , Nordestgaard Børge Grønne , Kanstrup Helle Lynge , Thomsen Kristian Korsgaard , Bech Jan , Bang Lia Evi , Henriksen Finn Lund , Andersen Lars Juel , Gohr Thomas , Larsen Linnea Hornbech , Soja Anne Merete Boas , Elpert Frank-Peter , Jakobsen Tomas Joen , Sjøl Anette , Joensen Albert Marni , Klausen Ib Christian , Schmidt Erik Berg , Bork Christian Sørensen
Published: October 2023

Context

Cholesterol carried in lipoprotein(a) adds to measured low-density lipoprotein cholesterol (LDL-C) and may therefore drive some diagnoses of clinical familial hypercholesterolemia (FH).

Objective

We investigated plasma lipoprotein(a) in individuals referred to Danish lipid clinics and evaluated the effect of plasma lipoprotein(a) on a diagnosis of FH.

Methods

Individuals referred to 15 Danish lipid clinics who were suspected of having FH according to nationwide referral criteria were recruited between September 1, 2020 and November 30, 2021. All individuals were classified according to the Dutch Lipid Clinical Network criteria for FH before and after LDL-C was adjusted for 30% cholesterol content in lipoprotein(a). We calculated the fraction of individuals fulfilling a clinical diagnosis of FH partly due to elevated lipoprotein(a).

Results

We included a total of 1166 individuals for analysis, of whom 206 fulfilled a clinical diagnosis of FH. Median lipoprotein(a) was 15 mg/dL (29 nmol/L) in those referred and 28% had lipoprotein(a) greater than or equal to 50 mg/dL (105 nmol/L), while 2% had levels greater than or equal to 180 mg/dL (389 nmol/L). We found that in 27% (55/206) of those fulfilling a clinical diagnosis of FH, this was partly due to high lipoprotein(a).

Conclusion

Elevated lipoprotein(a) was common in individuals referred to Danish lipid clinics and in one-quarter of individuals who fulfilled a clinical diagnosis of FH, this was partly due to elevated lipoprotein(a). These findings support the notion that the LPA gene should be considered an important causative gene in patients with clinical FH and further support the importance of measuring lipoprotein(a) when diagnosing FH as well as for stratification of cardiovascular risk.
Short-Term Pain Outcomes and Pain Medication Utilization Among Urine Toxicology-Identified Opioid and Marijuana Users After Elective Spine Surgery
Authors: Singh Manjot , Bajaj Ankush , Shlimak Anna , Kanekar Samika , Rampichini Margherita , Gokaslan Ziya L. , Scarfo Keith-Austin , Leary Owen P. , Guglielmo Maria A.
Published: October 2023

BACKGROUND AND OBJECTIVES:

Postoperative pain outcomes may be influenced by preoperative substance use, which is often underreported due to associated stigma. This study examined the impact of urine toxicology-identified preoperative opioid and marijuana use on pain outcomes after elective spinal surgery.

METHODS:

Patients undergoing elective spinal surgery between September 2020 and May 2022 were recruited for this prospective cohort study. Detailed chart review was completed to collect demographic, urine toxicology, Visual Analog Scale (VAS), and pain medication data. Comparisons between self-reported and urine toxicology-identified substance use, preoperative/postoperative VAS ratings, and postoperative pain medication use were made using χ2 tests, Student t-tests, and logistic regression, respectively. Models were adjusted for age, sex, and race.

RESULTS:

Among 111 participants (mean age 58 years, 59% female, 95% with ≥1 comorbidity), urine toxicology overestimated drug use (47% vs 16%, P < .001) and underestimated alcohol use (16% vs 56%, P < .001) at preoperative baseline relative to patient reports. Two weeks postoperatively, participants with preoperative opioid metabolites reported no significant improvements in pain from baseline (6.67 preoperative vs 5.92 postoperative, P = .288) unlike nonusers (6.56 preoperative vs 4.61 postoperative, P < .001). They also had worse postoperative VAS (5.92 vs 4.61, P = .030) and heavier reliance on opioid medications (odds ratio = 3.09, 95% CI = 1.21-7.89, P = .019). Conversely, participants with preoperative marijuana reported similar improvements in pain from baseline (users: 6.88 preoperative vs 4.36 postoperative, P = .001; nonusers: 6.49 preoperative vs 5.07 postoperative, P = .001), similar postoperative pain (4.36 vs 5.07, P = .238), and similar postoperative reliance on opioid medications (odds ratio = 0.96, 95% CI = 0.38-2.44, P = .928). Trends were maintained among the 83 patients who returned for the 3-month follow-up.

CONCLUSION:

Although urine toxicology-identified preoperative opioid use was associated with poor postoperative pain relief and reliance on postoperative opioids for pain management after elective spinal surgery, preoperative marijuana use was not. Preoperative marijuana use, hence, should not delay or be a contraindication to elective spinal surgery.
Guidelines to Implement Resistance Training in the Transfemoral and Transtibial Amputee
Authors: Schroeder Nicole , Anderson Stefanie
Published: October 2023

Apply It!

By reading this article, the health and fitness professional will learn guidelines and differences on how to implement a resistance training program for the transfemoral and transtibial prosthesis wearer.
The genome sequence of the Small Birch Bell, Epinotia ramella (Linnaeus, 1758)
Authors: Boyes Douglas , Lees David C. , Hammond James ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Natural History Museum Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: October 2023

We present a genome assembly from an individual female Epinotia ramella (the Small Birch Bell; Arthropoda; Insecta; Lepidoptera; Tortricidae). The genome sequence is 782.0 megabases in span. Most of the assembly is scaffolded into 28 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 15.44 kilobases in length. Gene annotation of this assembly on Ensembl identified 20,893 protein coding genes.
Implementation of the Requirements of the Updated Standard of Secondary General Education When Teaching the Topics of the Section �Polyhedra�
Authors: Vasileva M.
Published: October 2023

The article is based on the main key ideas of the formation of the planned subject and meta-subject results. The article discusses the methodology for implementing the requirements of the updated standard, taking into account the goals of teaching mathematics, under which conditions are created that ensure the possibility of forming students planned results in accordance with the requirements of the standard. An approach is proposed to the formation of individual skills of cognitive universal educational actions of students when teaching the topics of the polyhedra section, using educational tasks and training tasks that develop the ability to solve a wide range of problems.
Training of the safe and environment-friendly production house at koro benguk tempeh industry in Mertelu Village, Gedangsari District, Gunung Kidul
Authors: Utami Nurul Putrie , Setyawati Rani , Pratiwi Ima
Published: October 2023

Food is a basic need for humans need to live and support health. However, foods are needed to be processed safely, so it can fulfill nutritional needs and also maintain human health. Unsafe food processing can endanger humans because of the increased risk of foodborne disease. In Mertelu, Gedangsari, Gunung Kidul there is a small and medium enterprises (SMEs) that produces koro benguk tempeh. Unfortunately, the application of safe production houses and good processing methods have not been fully implemented in this industry. Thus, this program focused on increasing safe production house training which is one of the requirements for obtaining P-IRT certification. The activity was carried out for two days, 6th and 12th February 2020 with activities such as counseling, training, and mentoring in production houses. This activity was attended by Mertelu’s community who was involved in koro benguk tempeh production. After these programs, they was able to increase understanding of the safe management of production houses. However, some physical facilities were still inadequate to fulfill the standard because the resources limitation. Therefore, they are need further programs to improve existing infrastructure to meet the criteria for a safe food production house as a requirement of Household Food Food Industry (P-IRT) certification