bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the flexion relaxation ratio a reliable, valid, and responsive measure for individuals with and without non-specific spine pain? A systematic review and meta-analysis
Authors: De Carvalho Diana , Mackey Sarah , To Daphne , Summers Allyson , Frey Mona , Romme Kristen , Hogg-Johnson Sheilah , Howarth Samuel J.
Published: September 2023

This review sought to identify, critically appraise, compare, and summarize the literature on the reliability, discriminative validity and responsiveness of the Flexion Relaxation Ratio (FRR) in adults (≥ 18 years old) with or without spine pain (any duration), in either a clinical or research context. The review protocol was registered on Open Science Framework (https://doi.org/10.17605/OSF.IO/27EDF) and follows COSMIN, PRISMA, and PRESS guidelines. Six databases were searched from inception to June 1, 2022. The search string was developed by content experts and a health services librarian. Two pairs of reviewers independently completed titles/abstracts and full text screening for inclusion, data extraction, and risk of bias assessment (COSMIN RoB Toolkit). At all stages, discrepancies were resolved through consensus meetings. Data were pooled where possible with random effects meta-analyses and a modified GRADE assessment was used for the summary of findings. Following duplicate removal, 728 titles/abstracts and 219 full texts were screened with 55 included in this review. We found, with moderate certainty, that the cervical FRR has high test-retest reliability and lumbar FRR has moderate to high test-retest reliability, and with high certainty that the cervical and lumbar FRR can discriminate between healthy and clinical groups (standardized mean difference − 0.82 [95% CI -1.82, 0.17] and − 1.21 [-1.84, -0.58] respectively). There was not enough evidence to summarize findings for thoracic FRR discriminative validity or the standard error of measurement for the FRR in either the cervical, thoracic, or lumbar segments of the spine. Several studies that used FRR assumed responsiveness, but no studies were designed in a way that could confirm responsiveness. The evidence supports adequate reliability of FRR for the cervical and lumbar spine, and discriminative validity for the cervical and lumbar spine only. Improvements in study design and reporting are needed to strengthen the evidence base to determine the remaining measurement properties of this outcome.
The evaluation of a lean healthcare concept to improve the implementation of Digital Health innovations in secondary health care: a qualitative study within a Dutch hospital setting
Authors: Kellner Hanna A. , Edelman Eric R. , Eldik Nicole van , Hunen Perry , Spreeuwenberg Marieke
Published: September 2023

Background
Digital health innovations are considered a promising avenue in transforming the resourcing, organization and delivery of healthcare services and are often nurtured in organization based innovation labs. One of their biggest challenges is developing effective processes for sifting through ideas. To improve their existing work process, the Health Innovation Lab of the Maastricht University Medical Center + in The Netherlands took a lean approach. “Speed dating” was added to their innovation loop to optimize the contact between innovation owners and relevant experts. The aim of this research was to gain insight into the experiences and suggestions for improvement of this speed dating concept among the involved stakeholders.
Methods
A qualitative study was performed based on a focus group and semi-structured interviews. 36 stakeholders were selected by purposive sampling and approached to participate in this study. Data was collected from 11 respondents. The transcripts of the focus group and interviews were coded according to the open and axial coding phases of the methods of Grounded Theory.
Results
Five major themes emerged during the thematic analysis of the transcriptions: (1) Preparation before the Sign in, (2) Mapping out the process between Sign in and Sign out, (3) Defining the roles and deliverables of experts, (4) Guiding the idea owner, and (5) Supporting capacity of resources.
Conclusions
Since communication and collaboration to access external expertise and resources is so crucial to the success of the innovation lab’s process, it is perhaps not surprising that the most important improvements suggested by our results are associated with improving cooperation. We recommend large organizations, such as a secondary healthcare center, to examine the possibilities to introduce a similar process as the speed dating concept. Our results confirm the advantages of such an approach, but also highlight the necessity of continuous improvement. These improvements should focus on the coordination of joint efforts between stakeholders and the securing of resources. Therefore, we recommend focusing on clarifying the roles and deliverables of the experts, assisting the idea owner with project management and adding a sponsor who would be able to acquire specific resources.
Inhibition of STAT3 by 2-Methoxyestradiol suppresses M2 polarization and protumoral functions of macrophages in breast cancer
Authors: Deswal Bhawna , Bagchi Urmi , Santra Manas Kumar , Kapoor Sonia , Garg Manoj
Published: September 2023

Background
Breast cancer metastasis remains the leading cause of cancer-related deaths in women worldwide. Infiltration of tumor-associated macrophages (TAMs) in the tumor stroma is known to be correlated with reduced overall survival, and inhibitors of TAMs are sought after for reprogramming the tumor microenvironment. 2-Methoxyestradiol (2ME2), a potent anticancer and antiangiogenic agent, has been in clinical trials for treatment of breast cancer. Here, we investigated the potential of 2ME2 in modulating the pro-tumoral effects of TAMs in breast cancer.
Methods
THP-1-derived macrophages were polarized to M2 macrophages with or without 2ME2. The effect of 2ME2 on M2 surface markers and anti-inflammatory genes was determined by Western blotting, flow cytometry, immunofluorescence, and qRT‒PCR. The effect of M2 macrophages on malignant properties of breast cancer cells was determined using colony formation, wound healing, Transwell, and gelatin zymography assays. An orthotopic model of breast cancer was used to determine the effect of 2ME2 on macrophage polarization and metastasis in vivo.
Results
First, our study found that polarization of THP-1 cells to alternatively activated M2 macrophages is associated with the reorganization of the microtubule cytoskeleton. 2ME2 depolymerized microtubules and reduced the expression of CD206 and CD163, suggesting that it inhibits the macrophages to attain pro-tumoral M2 phenotype. Concurrently, 2ME2 inhibited the expression of anti-inflammatory cytokines and growth factors, including CCL18, TGF-β, IL-10, FNT, arginase, CXCL12, MMP9, and VEGF-A, and hindered the metastasis-promoting effects of M2 macrophages. 2ME2 treatment reduced the expression of CD163 in tumors and inhibited tumor growth and lung metastasis in the orthotopic breast cancer model. Mechanistically, 2ME2 was found to decrease the phosphorylation and nuclear translocation of STAT3. Furthermore, we confirmed the STAT3 inhibition-mediated effects of 2ME2 by using colivelin (a STAT3 activator) which abrogated the effects of 2ME2 on STAT3 phosphorylation and nuclear translocation.
Conclusions
Our study presents novel finding on mechanism of 2ME2 from the perspective of its effects on TAMs via the STAT3 signaling in breast cancer. The data supports further clinical investigation of 2ME2 and its derivatives as therapeutic agents to modulate the tumor microenvironment and immune response in breast carcinoma.
Effects of the Highway Matrix on the Roadkill Patterns of the Crab-Eating Fox, Cerdocyon Thous (Linnaeus, 1766), in Northeastern Brazil
Authors: Tenorio José Cleiton Souza , Cruz Geyner Alves dos Santos , Silveira-Filho Vladimir da Mota , Alexandre Fernando da Silva , Gripp Tiago da Motta , de Araújo Bianca Gonzaga , de Lyra-Neves Rachel Maria , Junior Wallace Rodrigues Telino
Published: September 2023

The development of modern society depends on the connectivity of different regions, and in particular, the establishment of roads and highways. While roads may be fundamental to development, they tend to have negative impacts on the biodiversity of a region. The present study verifies the roadkill patterns of the crab-eating fox, Cerdocyon thous, in the context of the characteristics of the surrounding matrix. Specimens were collected from four highways in the Brazilian states of Pernambuco and Alagoas, between August 2019 and December 2020. The date, time, and location of each specimen was recorded, and the carcasses were removed from the highway to avoid replicating records. A total of 101 specimens were collected, with a 1:1 sex ratio. Roadkill hotspots were observed in environments to which C. thous is adapted, in particular open fields and the margins of areas with denser vegetation. Rainfall may influence the observed roadkill patterns, given that the hotspots coincided with areas that have annual rainfall of between 600 mm and 700 mm. The molecular analyses indicated that the sample collected encompasses individuals from two distinct genetic groups, which are both distributed throughout the study area, reflecting its reduced genetic diversity. This scenario is influenced by factors such as the pattern of anthropogenic impacts within the study area and the ecological characteristics of the species. The impacts of the roadkill hotspots can be mitigated by measures such as signposting during recruitment periods.
Causal association between body mass index and risk of perianal abscess: A Mendelian randomization study
Authors: Wu Long , Wu Huan , Huang Fei , Li Xiaoyun , Zhen Yunhuan , Li Haiyang
Published: September 2023

Background
Perianal abscess is a common infectious disease affecting the perianal region. Body mass index (BMI) is a widely used indicator for assessing weight and obesity. Although obesity is known to be associated with multiple health issues, the understanding of the relationship between BMI and perianal abscess is limited. Whether BMI influences the risk of perianal abscess remains a subject of debate.
Method
A two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, weighted mode and MR-Egger regression methods was performed. We used the publicly available summary statistics data sets of genome-wide association studies (GWAS) meta-analyses for BMI in individuals of South Asian (n = 8,658) as the exposure and a GWAS for abscess of anal and rectal regions from the individuals included in OpenGWAS database (total n = 183 710; case = 1 287, control = 182 423) as the outcome.
Results
We selected 29 single nucleotide polymorphisms (SNPs) at genome-wide significance from GWASs on BMI as the instrumental variables. The IVW method showed there is no evidence to support a causal association between BMI and perianal abscess (Beta = -0.093, SE = 0.097, P = 0.340). MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept = 0.024; P = 0.285), and it also showed no causal association between BMI and perianal abscess (Beta = -0.254, SE = 0.177, P = 0.162). Moreover, the weighted median and weighted mode also approach no evidence of a causal association between BMI and perianal abscess (weighted median: Beta =- 0.126, SE = 0.139, P = 0.363; weighted mode: Beta = -0.207, SE = 0.182, P = 0.813). Cochran's Q test and the funnel plot indicated no evidence of heterogeneity and asymmetry, indicating no directional pleiotropy.
Conclusion
The results of MR analysis did not yield sufficient evidence to suggest a causal association between BMI and an elevated risk of perianal abscess.
Trainees’-supervisor collaboration, progress-visualisation, and coaching: a survey regarding challenges in ICU-trainees’ assessment
Authors: Scholte Johannes B.J. , Strehler Johannes Ch. , Dill Tatjana , Mook Walther N.K.A. van
Published: September 2023

Background Trainees’ assessment is needed, yet challenging, to achieve competence development. To improve the assessment process, it is important to identify its contributing and influencing factors. Methods Intensive care unit (ICU)-residents, -fellows, and intensivists from a large non-university hospital were surveyed about the challenges in assessing ICU-trainees. Thematic analysis revealed three major themes. Results Out of 45 physicians, 37(82%) responded. The first theme is trainee-intensivist collaboration discontinuity. The limited time the trainees stay the ICU, the large size of the team working in a discordant three-shift-system, and busy and unpredictable day-planning hinder sustained collaboration. A short briefing before collaboration, shared bedside care, and debriefing after collaboration with assessment and reflection upon collaboration were provided as potential solutions. Trial registration N/A
Structural basis for an early stage of the photosystem II repair cycle in Chlamydomonas reinhardtii
Authors: Liu Zhenfeng , Li Anjie , You Tingting , Pang Xiaojie , Wang Yidi , Tian Lijin , Li Xiaobo
Published: September 2023

Photosystem II (PSII) catalyzes water oxidization and plastoquinone reduction by utilizing light energy. It is highly susceptible to photodamage under high-light conditions and the damaged PSII needs to be restored through a process known as the PSII repair cycle. The detailed molecular mechanism underlying the PSII repair process remain mostly elusive. Here we report biochemical and structural features of a PSII-repair intermediate complex, likely arrested at an early stage of the PSII repair process in the green alga Chlamydomonas reinhardtii. The complex contains three protein factors associated with a damaged PSII core, namely Thylakoid Enriched Factor 14 (TEF14), Photosystem II Repair Factor 1 (PRF1), and Photosystem II Repair Factor 2 (PRF2). TEF14, PRF1 and PRF2 may function to facilitate release of the manganese-stabilizing protein PsbO, disassembly of peripheral light-harvesting complexes from PSII and blockage of the QB site, respectively. Moreover, an α-tocopherol quinone molecule is located adjacent to the heme group of cytochrome b559, potentially fulfilling a photoprotective role by preventing generation of reactive oxygen species.
Resveratrol Promotes Proliferation and Differentiation of Pre-osteoblast MC3T3-E1 cells by Preventing Apoptosis
Authors: Cai Weiye , Song Chao , Liu Fei , Chen Rui , Gao Silong , Guo Daru , Mou Ning , Yang Chun , Xiong Zhongwei , Liu Zongchao
Published: September 2023

The purpose of this study was to investigate the mechanism by which resveratrol (Res) inhibits apoptosis and promotes proliferation and differentiation of pre-osteoblastic MC3T3-E1 cells, laying the groundwork for the treatment of osteoporosis (OP). The TCMSP database was used to find the gene targets for Res. The GeneCards database acquire the gene targets for OP. After discovering the potential target genes, GO, KEGG, and Reactome enrichment analysis were conducted. Verifying the major proteins involved in apoptosis can bind to Res using molecular docking. CCK8 measured the proliferative activity of mouse pre-osteoblasts in every group following Res intervention. Alkaline phosphatase staining (ALP) and alizarin red staining to measure the ability of osteogenic differentiation. RT-qPCR to determine the expression levels of Runx2 and OPG genes for osteogenic differentiation ability of cells. Western blot to measure the degree of apoptosis-related protein activity in each group following Res intervention. The biological processes investigated for GO of Res therapeutic OP involved in cytokine-mediated signaling pathway, negative regulation of apoptotic process, Aging, extrinsic apoptotic signaling pathway in absence of ligand, according to potential therapeutic target enrichment study. Apoptosis, FoxO signaling pathway, and TNF signaling pathway are the primary KEGG signaling pathways. Recactome pathways are primarily engaged in Programmed Cell Death, Apoptosis, Intrinsic Apoptotic Pathway, and Caspase activation via extrinsic apoptotic signaling pathways. This research established a new approach for Res treatment of OP by demonstrating how Res controls the apoptosis-related proteins TNF, IL6, and CASP3 to suppress osteoblast death and increase osteoclastogenesis.
Insomnia in cancer patients: a systematic literature review
Authors: Chekani Farid , Lipschitz Alan , Mensah-Osman Edith
Published: September 2023

PURPOSE
Cancer patients often experience insomnia which can remain undetected in clinical practice, exacerbating mood disturbance, fatigue, and immunosuppression and impacting quality of life (QoL) and treatment outcomes. This review aimed to identify risk factors for insomnia and susceptible populations among cancer patients, and to quantify the impact of insomnia on QoL.
METHODS
This systematic review utilized pre-defined search criteria to identify studies related to the epidemiology and humanistic impact of insomnia in adult (≥ 18 years) cancer patients and their caregivers in the Medline and EMBASE databases.
RESULTS
Search terms identified 1,371 publications; 82 of these met the inclusion criteria. The studies showed that insomnia was prevalent throughout patients’ cancer journeys. Insomnia often preceded the diagnosis of cancer by months and persisted for several years after treatment. Breast cancer was the tumor type with the most reports of insomnia. Insomnia substantially impacted patients’ QoL. Subgroups who might benefit most from treatment for insomnia were those receiving chemotherapy and those with comorbid psychological symptoms such as anxiety and depression. For many tumor types and patient populations there were few or no studies of insomnia.
CONCLUSIONS
The medical literature reports that insomnia is highly prevalent in cancer patients, and significantly affects their QoL. Detecting and treating insomnia should be an element in the comprehensive care of cancer patients, to improve their physical health, and emotional well-being and QoL.
Multiwavelength Constraints on the Origin of a Nearby Repeating Fast Radio Burst Source in a Globular Cluster
Authors: Pearlman Aaron , Scholz Paul , Bethapudi Suryarao , Hessels Jason , Kaspi Victoria , Kirsten Franz , Nimmo Kenzie , Spitler Laura , Fonseca Emmanuel , Meyers Bradley , Stairs Ingrid , Tan Chia Min , Bhardwaj Mohit , Chatterjee Shami , Cook Amanda , Curtin Alice , Dong Fengqiu , Eftekhari Tarraneh , Gaensler Bryan , Guver Tolga , Kaczmarek Jane , Leung Calvin , Masui Kiyoshi , Michilli Daniele , Prince Thomas , Sand Ketan , Shin Kaitlyn , Smith Kendrick , Tendulkar Shriharsh
Published: September 2023

Since fast radio bursts (FRBs) were discovered, their precise origins have remained a mystery. Multiwavelength observations of nearby FRB sources provide one of the best ways to make rapid progress in our understanding of the enigmatic FRB phenomenon. We present results from a sensitive, broadband multiwavelength X-ray and radio observational campaign of FRB 20200120E, the closest known extragalactic repeating FRB source. At a distance of 3.63 Mpc, FRB 20200120E resides in an exceptional location, within a ~10 Gyr-old globular cluster in the M81 galactic system. We place deep limits on both the persistent X-ray luminosity and prompt X-ray emission at the time of radio bursts from FRB 20200120E, which we use to constrain possible progenitors for the source. We compare our results to various classes of X-ray sources and transients. In particular, we find that FRB 20200120E is unlikely to be associated with: ultraluminous X-ray bursts (ULXBs), similar to those observed from objects of unknown origin in other extragalactic globular clusters; giant flares, like those observed from Galactic and extragalactic magnetars; or most intermediate flares and very bright short X-ray bursts, similar to those seen from magnetars in the Milky Way. We show that FRB 20200120E is also unlikely to be powered by a persistent or transient ultraluminous X-ray (ULX) source or a young, extragalactic pulsar embedded in a Crab-like nebula. We also provide new constraints on the compatibility of FRB 20200120E with accretion-based FRB models involving X-ray binaries and models that require a synchrotron maser process from relativistic shocks to generate FRB emission. These results highlight the power that multiwavelength observations of nearby FRBs can provide for discriminating between potential FRB progenitor models.
Rheumatoid Arthritis and Gastroesophageal Reflux Disease: A Bidirectional and Multivariable Two-sample Mendelian Randomization Study
Authors: Wang Haifan , Dang Xiaoqian , Wang Haoyu
Published: September 2023

Aims/hypothesis: The association between Gastroesophageal Reflux Disease (GERD) and Rheumatoid Arthritis (RA) has been reported by many observational studies in the Asian population. Here, we examined the bidirectional causal effects between GERD and RA by two sample MR analyses using genetic evidence. Methods: Two-sample Mendelian randomization analyses were performed to determine the causal effect of the GERD (129080 cases vs 602604 control participants) on RA (6236 cases vs 147221 control participants) and RA on GERD respectively. The inverse-variance weighted (IVW) method was used as the primary analysis. Weighted median and MR-Egger regression were taken as supplements. The Cochran Q test evaluated the heterogeneity. Horizontal pleiotropy was detected by estimating the intercept term of MR-Egger regression. Further, multivariable MR analyses were performed to exclude the influence of confounding factors including years of schooling, BMI, and time spent watching television between GERD and RA. Result: Both The univariate MR (UVMR) and multivariable MR (MVMR) provided strong evidence that the RA was causally and positively influenced by GERD (UVMR: OR = 1.49, 95% CI = 1.25–1.76, P = 6.18*10− 6; MVMR: OR = 1.69, 95% CI = 1.24–2.31, P = 8.62*10− 4), while GERD was slightly influenced by RA (UVMR: OR = 1.03, 95% CI = 1.00-1.06, P = 0.042; MVMR: OR = 1.04, 95% CI = 1.00-1.07, P = 0.0271). Conclusion: Our comprehensive bidirectional MR analysis found that for the European population, GERD can induce the occurrence of RA (OR = 1.69, P < 0.00125), while RA only has a slight influence on GERD. Specifically, GERD patients are suffering a 69% increased risk of RA occurrence, which means GERD is a substantial risk factor for RA.
Perception, Sentiments, and the Level of Awareness toward the Dental Implant among General Population in Sulaimaniyah City, Iraq
Authors: Amin Nzar Abdulqadr Muhammed
Published: September 2023

Background:Edentulism is one of the most commonly encountered conditions affecting the oral cavity. Dental implants have emerged as a widely accepted treatment option prosthodontically. However, lack of public awareness and the cost of the treatment act as barriers to limit their applicability.Objectives:To investigate the perception, sentiments and level of awareness toward the dental implant among the general population in Sulaimaniyah City, Iraq.Materials and Methods:A questionnaire-based survey was conducted on 1132 participants in Sulaimaniyah City, Iraq, from February 15, 2023, till August 15, 2023, to collect their sociodemographic data, knowledge and attitudes toward dental implants for their missing tooth/teeth.Results:The mean age of participants was 41.3±14.6 years, and most (30.7%) belong to the age group 31 - 44 years. Also, most of them were males (63.6%), married (75.3%), educated (91.3%), from rural areas (82.3%), and had >1 missing tooth (75%). Regarding the participants' knowledge of dental implants, most had information (78.4%) /heard about it (83.3%), mainly from dentists (43.6%); however, least of them (21.5%) /their family members (43%) had replaced missing teeth by dental implants. Additionally, the participant's attitudes toward the dental implant indicated that most of them were interested in replacing their missing teeth (88.8%) but did not do it due to financial reasons (87%) and considered replacement as a very important (92.5%) and safe process (79.2%). Also, most of them thought there was no substantial difference between artificial and natural tooth appearance/function (47.9%), preferred the conventional method for dental implant (47.7%), and would like to do an implant due to problems in dental appearance, speech, or dental function (81.5%). Finally, significant/highly significant differences were seen between each participant's factor (age, gender, marital status, education level, and residency) with most items of attitude/awareness toward dental implants.Conclusions:Most participantswere aware of the knowledge and attitude of dental implant for replacing missing tooth/teeth, especially males, married ones, educated individuals, and those from urban area; however, financial problem is the main obstacle. Additionally, the conventional method is preferable for replacing missing tooth/teeth using dental implants among studied individuals.
Analysis of Women's Menstrual Changes after COVID-19 Infection: a Descriptive Study
Authors: Han Ruxue , Jiang Xiaolin , Yang Xin
Published: September 2023

Background: In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. Since December 2022, China has adjusted anti-epidemic policies and a large-scale COVID-19 infection has emerged. We aimed to explore the menstrual changes of women before and after infection with the COVID-19.
Methods: This study was designed as a descriptive, cross-sectional study. We collected data from participants infected with COVID-19 from January 1, 2023 to March 1, 2023 by issuing electronic questionnaires. Women were invited to fill out the questionnaire about their menstrual characteristic after COVID-19 infection.
Results: A total of 884 women with COVID-19 infections participated in the study. 662(74.9%) participants experienced changes in one or more of menstrual characteristics. Cycle length seemed to be the characteristic most likely to change (47.6%), followed by menstrual flow (41.7%), duration of menstrual periods (29.5%), degree of dysmenorrhea (29.0%) and intermenstrual bleeding (14.9%). The main clinical manifestations were menstruation delayed (26.3%), menstrual flow decreased (25.5%), dysmenorrhea relief (21.9%) and menstruation prolonged (21.0%). And we found new intermenstrual bleeding in 8.4% participants after COVID-19 infection. The menstrual change rate of the irregular menstrual group was significantly higher than that of the regular menstrual group (73.0% vs. 62.3%, P＜0.001).
Conclusions: COVID-19 infection may cause menstrual changes in most women. It is important to be aware of the menstrual changes after COVID-19 infection and to inform women about this issue.
Learning to Express Reward Prediction Error-like Dopaminergic Activity Requires Plastic Representations of Time
Authors: Shouval Harel , Cone Ian , Clopath Claudia
Published: September 2023

The dominant theoretical framework to account for reinforcement learning in the brain is temporal difference (TD) reinforcement learning. The TD framework predicts that some neuronal elements should represent the reward prediction error (RPE), which means they signal the difference between the expected future rewards and the actual rewards. The prominence of the TD theory arises from the observation that firing properties of dopaminergic neurons in the ventral tegmental area appear similar to those of RPE model-neurons in TD learning. Previous implementations of TD learning assume a fixed temporal basis for each stimulus that might eventually predict a reward. Here we show that such a fixed temporal basis is implausible and that certain predictions of TD learning are inconsistent with experiments. We propose instead an alternative theoretical framework, coined FLEX (Flexibly Learned Errors in Expected Reward). In FLEX, feature specific representations of time are learned, allowing for neural representations of stimuli to adjust their timing and relation to rewards in an online manner. In FLEX dopamine acts as an instructive signal which helps build temporal models of the environment. FLEX is a general theoretical framework that has many possible biophysical implementations. In order to show that FLEX is a feasible approach, we present a specific biophysically plausible model which implements the principles of FLEX. We show that this implementation can account for various reinforcement learning paradigms, and that its results and predictions are consistent with a preponderance of both existing and reanalyzed experimental data.
Twin home birth: Outcomes of 100 sets of twins in the care of a single practitioner
Authors: Fischbein Stuart James , Freeze Rixa
Published: September 2023

Background:Research on outcomes of community (home or birth center) twin birth is scarce. This study evaluates the outcomes of twin pregnancies entering care with a single practitioner in a community setting.Methods:This is a retrospective observational cohort study of 100 consecutive twin pregnancies planning community births during 12 years with a single obstetrician. Outcomes measured included mode of delivery; birth weights; Apgar scores; ante-, intra-, and post-partum transports; perineal integrity; delivery interval; blood loss; chorionicity; weight concordance; and other maternal or neonatal morbidity.Results:Of the 100 twin pregnancies who entered into care, 31 (31%) transferred to a hospital-based clinician prior to labor. The remaining 69 sets of twins were still in the obstetrician’s care at the onset of labor. Of those 69 pregnancies, 79.7% (n=55) were di-amniotic-di-chorionic and 21.3% (n=14) were mono-di. The vaginal delivery rate was 91.3% (n=63) including 16/21 primips/TOLACs (76.2%) and 47/48 multips (97.9%); 6 mothers (8.7%) had in-labor cesareans (1 multip and 5 primips). Rates of vaginal delivery did not vary significantly by chorionicity; 91.4% (53/58) of di-di and 90.9% (10/11) of mono-di twins gave birth vaginally.There were 8 transports in labor (11.6%) with 2 birthing vaginally and 6 via cesarean. Average gestational age was 39.0 weeks (range 35-42). Compared to primiparas, multiparas had less perineal trauma and higher rates of community, vaginal, and spontaneous vaginal birth. One twin infant and one mother required postpartum hospital transport. Of the babies born in a community setting, there was no serious morbidity requiring hospital treatment.Conclusions: A community birth leads to high rates of vaginal birth and good outcomes for both mothers and babies in properly selected twin pregnancies. Community twin birth with midwifery style care under specific protocol guidelines and with a skilled practitioner may be a reasonable choice for women wishing to avoid a cesarean section—especially when there is no option of a hospital vaginal birth. However, this study is underpowered to calculate uncommon adverse neonatal outcomes. Training of future practitioners in vaginal twin and breech birth skills remains an imperative.
High-entropy CoCrFeMnNi/B2 structure aluminide-laminated composites with enhanced mechanical properties
Authors: Wang Yu , Peng Xiangfei , Fallatah Ahmed M. , Qin Hongxing , Zhao Wenjuan , Zaki Zaki I. , Xu Hong , Liu Bin , Mao Hongkui , El-Bahy M. , Algadi Hassan , Wang Chao
Published: September 2023

CoCrFeMnNi-based high-entropy/B2 structure aluminide-laminated composites were produced via the hot pressing diffusion sintering method at 1000 ℃. The results revealed that the aluminide structure layer based on the Al13(Cr, Mn, Fe, Co, Ni)4 phase first transforms into Al8(Cr, Mn, Fe, Co, Ni)5 phases with a trigonal crystal structure and then gradually transitions into Al(Cr, Mn, Fe, Co, Ni) phases with a B2 cubic crystal structure under high-temperature annealing. During high-temperature annealing, the elements Ni, Co, and Fe exhibit higher diffusion rates and diffusion amounts in the aluminide layer. The transformation of the aluminide layer is mainly influenced by the diffusion behavior of these elements. The absence of an oxidation interface barrier during high-temperature annealing results in multiple diffusion mechanisms, leading to the predominance of lattice diffusion and interface diffusion, which control the growth kinetic of the Al(Cr, Mn, Fe, Co, Ni) phase layer. The hardness indentation of the B2-Al(Cr, Mn, Fe, Co, Ni) phases, obtained by high-temperature annealing, shows no cracks and exhibits a multi-slip system characteristic of ductile aluminum compounds. This ductile behavior helps to reduce the deformation resistance in the hard and brittle layer and decreases the likelihood of delamination failure during plastic deformation. The bending strength of high-entropy/aluminide-layered (HAL) composite materials after high-temperature annealing reaches 1000 MPa, with the main energy dissipation modes being the plastic deformation of ductile layer and fracture of the hard and brittle layer. Dynamic impact failure forms mainly include plastic deformation and delamination, with impact strength and energy consumption reaching 2317 MPa and 4750 J/mm3, respectively. This study provides phase formation sequence and dynamic mechanical properties of High-entropy CoCrFeMnNi/B2 structure aluminide-laminated composites which proved to be a new type of composites with good impact resistance.
A neuronal relay mediates muscle-adipose communication that drives systemic metabolic adaptation to high-sugar diets
Authors: Rewitz Kim , Kubrak Olga , Joergensen Anne , Koyama Takashi , Nagy Stanislav , Lassen Mette , Hald Jacob , Madsen Dennis , Halberg Kenneth , Texada Michael , Hansen Jakob
Published: September 2023

Obesity leads to impaired insulin signaling and tissue sensitivity, which drive the onset of type 2 diabetes. Insulin resistance leads to a reduction in cellular glucose uptake, resulting in elevated blood glucose levels, which consequently cause β-cell dysfunction and development of diabetes. Although improving insulin signaling is a key target for restoring whole-body glucose homeostasis and reversing diabetes, the multi-organ mechanisms that regulate insulin signaling and tissue sensitivity are poorly defined. We screened the secretome and receptome in Drosophila to identify the underlying interorgan hormonal crosstalk affecting diet-induced insulin resistance and obesity. We identified complex interplay between muscle, neuronal, and fat tissues, mediated by the conserved BMP and LGR signaling pathways, which augments insulin signaling and improves dietary sugar tolerance. We found that muscle-derived BMP signaling is induced by sugar and governs neuronal Bursicon signaling. Acting through its LGR-family receptor, Bursicon both enhances insulin secretion and improves insulin sensitivity in adipose tissue, thereby preventing sugar-induced hyperglycemia. Inhibition of Bursicon-LGR signaling in adipose tissue exacerbates sugar-induced insulin resistance, and we discovered that this condition could be alleviated by suppressing NF-κB signaling. Our findings identify a muscle-neuronal-fat tissue axis that drives metabolic adaptation to high-sugar conditions by modulating insulin secretion and adipocyte insulin sensitivity, highlighting mechanisms that may be exploited for the development of strategies for the treatment and reversal of insulin resistance.
Development, Implementation, and Evaluation of Entrustable Professional Activities (EPAs) for Medical Radiation Technologists in Taiwan: A Nationwide Experience
Authors: Wen Shu-Yu , Tu Chun-Yuan , Huang Tzu-Jie , Cheng Ching-Hsueh , Liu Cheng-Heng , Lu Szu-Huai , Tsai Chiao-Ling , Huang Kuo-Ming , Yang Chih-Wei
Published: September 2023

Background:
Competency-based medical education (CBME) is an outcomes-oriented approach focused on developing competencies that translate into clinical practice. Entrustable professional activities (EPAs) bridge competency assessment and clinical performance by delineating essential day-to-day activities that can be entrusted to trainees. EPAs have been widely adopted internationally, but not yet implemented for medical radiation professionals in Taiwan.
Materials and Methods:
A nationwide consensus process engaged 97 experts in radiation technology education representing diagnostic radiography, radiation therapy, and nuclear medicine. Preliminary EPAs were developed through nominal group technique and modified Delphi technique. Final EPAs were established through expert consensus meetings and evaluated for quality using the QUEPA and EQual tools. Additionally, 177 clinical staff were trained on EPA-based assessment.
Results:
Through iterative consensus building, 6 core EPAs with 18 component observable practice activities (OPAs) were developed, encompassing routines specific to each radiation technology specialty. QUEPA and EQual questionnaire data verified the EPAs were valid, reliable, and of high quality for clinical teaching and evaluation. Self-efficacy ratings demonstrated the training significantly improved clinical teachers’ EPA knowledge and implementation abilities across specialties.
Conclusion:
Consensus development of tailored EPAs and associated training enables rigorous competency assessment during medical radiation technology education in Taiwan. Further EPA expansion and training of clinical staff will enhance care quality by producing competent professionals.
scMultiSim: simulation of single cell multi-omics and spatial data guided by gene regulatory networks and cell-cell interactions
Authors: Zhang Xiuwei , Li Hechen , Zhang Ziqi , Squires Michael , Chen Xi
Published: September 2023

Simulated single-cell data is essential for designing and evaluating computational methods in the absence of experimental ground truth. Existing simulators typically focus on modeling one or two specific biological factors or mechanisms that affect the output data, which limits their capacity to simulate the complexity and multi-modality in real data. Here, we present scMultiSim, an in silico simulator that generates multi-modal single-cell data, including gene expression, chromatin accessibility, RNA velocity, and spatial cell locations while accounting for the relationships between modalities. scMultiSim jointly models various biological factors that affect the output data, including cell identity, within-cell gene regulatory networks (GRNs), cell-cell interactions (CCIs), and chromatin accessibility, while also incorporating technical noises. Moreover, it allows users to adjust each factor's effect easily. We validated scMultiSim’s simulated biological effects and demonstrated its applications by benchmarking a wide range of computational tasks, including multi-modal and multi-batch data integration, RNA velocity estimation, GRN inference and CCI inference using spatially resolved gene expression data, many of them were not benchmarked before due to the lack of proper tools. Compared to existing simulators, scMultiSim can benchmark a much broader range of existing computational problems and even new potential tasks.
Unraveling groundwater-stream connections at the continental scale
Authors: Yang Chen , Condon Laura , Maxwell Reed
Published: September 2023

Groundwater is a critical component of the terrestrial water cycle, yet the extent and depth of its connections with other hydrologic components, such as streamflow, remain unquantified. Here, we conducted a backward particle tracking simulation based on high-resolution integrated hydrologic modeling across the contiguous United States (CONUS). We quantified the lateral length and vertical depth of groundwater flow discharged to streams as baseflow. Our simulation results suggest that water may travel underground almost 240km to emerge in a stream and that lateral groundwater flow lengths longer than 50 km are common across North America. Confined groundwater, aquifers typically 10–100m below the ground surface, significantly contributes to baseflow. Boundaries of surface water and groundwater watersheds rarely match and only align at continental divides. Our results suggest that about one-quarter of the baseflow over CONUS is inter-basin groundwater flow and that water-balance approaches underestimate these quantities due to concurrent groundwater exportation and importation of a watershed. This nested nature of groundwater flow is an important characteristic that determines how far and how deep water flows to supply streamflow. Our findings have fundamental significance for understanding the movement of groundwater and its interactions with other hydrologic components in the terrestrial water cycle.
The Impact of psychological factors, depression, and anxiety on tobacco abuse in Primary Health Care adults: A Secondary Data Analysis
Authors: Méndez-López Fátima , Oliván-Blázquez Bárbara , Domínguez-García Marta , López-Del-Hoyo Yolanda , Rabanaque Isabel , Casado-Vicente Verónica , Martí-Lluch Ruth , Magallón-Botaya Rosa
Published: September 2023

Smoking is a growing public health issue that has a negative influence on social and psychological well-being. The presence of certain personal factors on health-promoting behavior influences mental well-being and less dependence on tobacco in the population. We aimed to explore the relationship between tobacco dependency, the degree of severity of anxious and depressive symptoms, and certain related personal characteristics and adult health behavior. This study includes 391 participants of 35– 74 years old from the lists of the primary health care centers located in Aragón (Spain). Data were analyzed using descriptive, bivariate, multivariate and mediation analysis. The primary variable was tobacco consumption, evaluated qualitatively (presence or absence) and quantitatively, as consumption measured through the number of cigarettes. High patient activation and health literacy were predictors of having a lower risk of being a smoker and lower daily cigarette consumption. However, being single and having more severe depressive symptoms were significantly higher predictors of smoking and higher daily cigarette consumption. The associations between the presence of tobacco dependence and the constructs of health literacy and patient activation, mediated by depression, were significant. The severity of depressive and anxious symptoms and personal factors are related to tobacco dependence. These correlations must be considered while developing particular preventative efforts to reduce population smoking rates.
Unravelling the Genetic Link: An Umbrella Review on HLA-B∗15:02 and Anti-Epileptic Drug-induced Stevens–Johnson Syndrome / Toxic Epidermal Necrolysis
Authors: Liu Wei Yang Christopher , tham Kar Mun , Yek Jia Lin Jacklyn
Published: September 2023

Purpose
This umbrella review was conducted to summarize the evidence between association between HLA*1502 allele with various antiepileptic induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
Methods
Pubmed, Scopus and EMBASE were searched for eligible reviews in May 2023. Study was registered in PROSPERO. Two authors independently screened titles and abstracts and assessed full-text reviews for eligibility. The quality of meta-analyses was appraised with AMSTAR-2 and the quality of case control studies were appraised with Newcastle- Ottawa Scale (NOS). Narrative summaries of each anti-epileptic drug were analysed. Pre-established protocol was registered on the International Prospective Register of Systematic Reviews database (ID: CRD42023403957).
Results
Included studies are meta-analyses and case control studies evaluating the association of HLA-B*1502 allele with the following antiepileptics: 7 meta-analyses for Carbamazepine (CBZ), 3 meta-analyses for Lamotrigine (LTG), 3 case-control studies for Oxcarbazepine (OXC), 9 case-control studies Phenytoin (PHT) and 4 case-control studies study for Phenobarbitone.
The findings of this umbrella review suggest that there is strong association between HLA B-1502 with SJS/TEN for Carbamazepine and Oxcarbazepine and a milder association for Lamotrigine and Phenytoin.
Conclusions
In summary, although HLA-B*1502 is less likely to be associated with Phenytoin or Lamotrigine -induced SJS/TEN compared to Carbamazepine-induced SJS/TEN, it is a significant risk factor which if carefully screened could potentially reduce development of SJS/TEN. In view of potential morbidity and mortality, HLA-B*1502 testing may be beneficial in patients who are initiating Lamotrigine / Phenytoin therapy. However, further studies are required to examine the association of other alleles with development of SJS/TEN and to explore the possibility of genome-wide association studies prior to initiation of treatment.
Development of a CT-based scoring system to predict progression after intraoperative radiotherapy in locally advanced pancreatic cancer with initial stable disease
Authors: Cai Wei , Zhu Yongjian , Teng Ze , Li Dengfeng , Cong Rong , Chen Zhaowei , Ma Xiaohong , Zhao Xinming
Published: September 2023

Objectives
We aimed to develop a risk scoring system integrating CT imaging features and serum carbohydrate antigen 19 − 9 (CA19-9) for stratifying the short-term outcomes in locally advanced pancreatic cancer (LAPC) patients receiving intraoperative radiotherapy (IORT) with initial stable disease (SD).
Materials and Methods
We retrospectively recruited 103 consecutive patients with LAPC who received IORT as first-line treatment. All patients underwent CT examinations and serum CA19-9 test baseline and post-IORT. Clinical and CT imaging features were analyzed. The risk scoring system was constructed using the coefficient of the independent risk factors for progression-free survival (PFS) from cox regression model. Time-dependent receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of the scoring system.
Results
All patients developed disease progression after IORT and the median PFS time was 6.40 (95% confidence interval [CI]:4.95–7.86) months. Multivariable analysis revealed that CA19-9 non-response (hazard ratio [HR] = 1.672, P = 0.018), the percentage change of relative enhanced ratio (HR = 2.318, P = 0.030), rim-enhancement (HR = 1.784, P = 0.007), and peripancreatic fat infiltration (HR, 1.799, P = 0.006) were significant correlated with poor PFS. Time-dependent ROC showed a satisfactory predictive performance for disease progress with area under the curve (AUC) all above 0.70. Low-risk patients (risk score < 5) progress significantly slower than high-risk patients (risk score ≥ 5) (P < 0.001).
Conclusion
The scoring system integrating CT imaging features and CA19-9 can be used as a convenient and practical method for prognosis prediction in LAPC patients showing SD receiving IORT.
Unsupervised machinery prognostics approach based on wavelet packet decomposition and variational autoencoder
Authors: de Godói Leonardo Franco , Nóbrega Eurípedes Guilherme de Oliveira
Published: September 2023

The prognosis of rotating machinery has been very prominent in recent years thanks to the advances in digital signal processing and intelligent systems. Unsupervised machine learning methods have been adopted along with signal processing techniques in both time and frequency domain to build indicators that describe the degradation of mechanical systems. This paper proposes a novel method for generating a degradation indicator for estimating the remaining useful life of rotating machinery critical components, based on a beta variational autoencoder neural network that processes statistical distributions in a feature hyperspace whose coordinates mix time-domain analysis and wavelet packet decomposition of vibration signals. Indicators are calculated using bearing vibration signals from a publicly available dataset, aiming to enhance the visibility of monotonic trends, and are used to assess different hyperparameter configurations of the proposed methodology. Based on the comparison with recently published results on the same dataset, the proposed method produced robust indicators capable of detecting early changes in degradation models, generating more accurate RUL estimates.