bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Pre-existing Mood Disorders on Patient-Reported Outcomes After Arthroscopic Rotator Cuff Repair
Authors: Davey Martin S. , Davey Matthew G. , Hurley Eoghan T. , Mullett Hannan
Published: October 2023

Background:

The purpose of this study was to systematically review the literature to evaluate the effect of pre-existing mood disorders on patient-reported outcomes after arthroscopic rotator cuff repair (ARCR).

Methods:

Two independent reviewers performed a literature search using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using PubMed, Embase, Cochrane Library, and Scopus databases. Only studies which grouped as either having a pre-existing mood disorder (namely anxiety and/or depression) or not and evaluated patient-reported outcomes following ARCR procedures were considered for inclusion. Meta-analysis was performed on outcomes using RevMan, with a p-value <0.05 being deemed statistically significant.

Results:

Our search found 8 studies including 1,166 shoulders (58.9% males), with an average age of 57.7 ± 3.2 years (21-81) and mean follow-up of 20.8 ± 16.7 months (3-77) which met our inclusion criteria. There were a total of 262 patients (22.5%; mean age 59.9 ± 1.4 years) with pre-existing anxiety and/or depression and 904 patients (77.5%; mean age 59.7 ± 1.7 years) in the control group who underwent ARCR, respectively. Meta-analysis found significantly lower American Shoulder and Elbow Surgeons scores as well as Simple Shoulder Test scores in patients with pre-existing anxiety and/or depression when compared with a control (mean difference [MD] −7.92 [−9.45, −6.40], p < 0.0001, I2 = 0%; MD −1.56 [−2.54, −0.59], p = 0.002, I2 = 80%, respectively) In addition, meta-analysis demonstrated significantly higher Visual Analog Scale scores for pain in patients with pre-existing anxiety and/or depression when compared with a control (MD 0.70 [0.02, 1.38], p = 0.04, I2 = 71%). Furthermore, meta-analysis performed found that ARCR resulted in significant changes in the rates of reported anxiety and/or depression in patients with pre-existing anxiety and/or depression (MD 4.06[−2.47, 6.68], p < 0.0001, I2 = 0%).

Conclusion:

Our review found that patients with pre-existing mood disorders were significantly more likely to report higher rates of postoperative pain and poorer functional outcomes following ARCR procedures, when compared with controls without mood disorders. Therefore, the presence of pre-existing anxiety and/or depression warrants consideration in the management paradigm for patients with rotator cuff tears. More optimistically, however, ARCR resulted in significant improvements in anxiety and/or depressive symptoms postoperatively.

Level of Evidence:

Level III; systematic review of retrospective comparative studies. See Instructions for Authors for a complete description of levels of evidence.
A Study on the Legality of Trap Investigation for Drug Crimes
Authors:   Korean Association of Public Safety and Criminal Justice, Ha Tae-In
Published: October 2023

Article 12 (1) of the Korean Constitution accepts the principle of due process as a constitutional principle. The principle of due process stipulates the basic principle that criminal proceedings should be regulated in terms of guaranteeing basic rights. Therefore, if the investigation by the investigative agency violates the principle of due process, it is illegal. An investigation may conduct an investigation necessary to achieve its purpose (Article 199 (1) of the Criminal Procedure Act).
However, even if the necessity of such an investigation is recognized, it cannot be allowed if the means of the investigation are not equivalent to the purpose. As a general principle of investigation, the principle of considerability of investigation or proportionality of investigation is derived from the principle of due process. Specifically, the means should be suitable for achieving the purpose of the investigation (the principle of suitability), and the necessary means with the least infringement (the principle of minimum infringement), and there should be a balance between the benefits of achieving the purpose of the investigation and the benefits infringed by the investigation (the principle of balance).
Currently, drug crimes have difficulties in detecting criminals and collecting evidence due to the wider area and the trend of intelligence due to informatization. As a means of this, the need for a trap investigation will increase further. Nevertheless, it should be legally allowed only to the extent that it complies with the principle of due process and the principle of considerability or proportionality of investigation under Article 12 (1) of the Constitution.
Legal Issues and Comments on the Railway Special Judicial Police System
Authors:   Korean Association of Public Safety and Criminal Justice, Jung Se Jong , Park Jae Poong
Published: October 2023

This paper was designed to derive legal issues on the railway special judicial police system, present comments on them, and ultimately promote policy suggestions.
The main issues can be summarized as the appropriateness of the name, the basis for the exercise of administrative police authority, competition under the jurisdiction of general police officers, and compliance with the principle of legal reservation.
The legal authority of the railway police was reviewed in the order of organizational laws, administrative police laws, judicial police laws, and administrative rules. And we looked at the cases of Britain, France, the United States, and Germany and drew implications.
Railway police in developed countries were given both administrative police power and judicial police power within their jurisdiction, and security guards were helping regular railway police officers.
The legal problems of the current railway special judicial police system are the railway police do not have a legal basis for exercising administrative police power and the Regulations on the Execution of Duties of Railway Judicial Police Officers are only administrative rules.
In this paper, five issues were derived and the following comments were developed.
First, the Railway Safety Act should be revised so that railway police can exercise their administrative police rights.
Second, it is necessary to upgrade the Regulations on the Execution of Duties of Railway Judicial Police Officers to the level of legal orders.
Third, There is a great need to reasonably coordinate object jurisdiction and regional jurisdiction with the general police.
Fourth, railroad operators should be obligated to operate security personnel.
Fifth, it is desirable to reorganize the organization of the Railway Bureau of the Ministry of Land, Infrastructure and Transport.
Optimization of unmanned aerial vehicle application for measuring in complex urban green space
Authors: Jin Rongye , Huang Jinyi , Xiao Xiangdong , Xu Yanjie
Published: October 2023

The main tree biometric variables of urban green space can derive indicators of multiple ecological benefit values. Compared with plantations and natural forests, urban green space is usually featured with higher tree richness, more complex landscape design, and a higher degree of spatial heterogeneity. Appropriate designs for flight variable settings in complex urban space can significantly improve the quality of data, and bring large differences in economic and time costs in practical applications. However, current studies have a limited understanding of flight variables setting for UAV applications in complex urban green spaces. We carried out rigorous and practical designs for flight variable settings with high-frequency UAV oblique image measurements. We tested and quantified the effect of the settings of main flight variables (i.e., flight altitude, image overlap, gimbal pitch and solar elevation) on the process data and final data quality in a representative complex urban green space. In the limited range of flight variable settings, the data accuracy is significantly different in the complex urban green space. We found that solar elevation is the most important factor affecting the data quality. Specifically, flight operations with a lower solar elevation provided a higher measurement accuracy and outstanding cost-effectiveness which is significantly different from the solar elevation setting for measuring in plantations. Our results (which are different from the previous study on homogenous green spaces) also suggested to avoid strong sunlight during flight operations and to ensure that the flight altitude is three to four times higher than the tallest tree at least to improve data quality. The settings of the image overlap and the gimbal pitch should take more time cost and economic benefits into consideration. This study demonstrated the feasibility of UAV applications in complex urban green spaces, and the impact and importance of each flight variable on the dataset quality. The systematic analysis, quantitative results, and exact visualizations can facilitate a wider application space (i.e., urban forestry, landscape ecology, urban planning and urban design) and higher application quality of UAV oblique in urban green space.
New Approaches to the Factors Contributing to Environmental Degradation: Do Financial Institutions and Markets Matter?
Authors: Tekin Bilgehan , Bekun Festus Victor
Published: October 2023

The authors have requested that this preprint be removed from Research Square.
What doesn’t break rock makes it tougher
Authors: Rasmussen Monica , Eppes Martha Cary , Mushkin Amit , Meredith Philip , Keanini Russell , Aldred Jennifer , Andričević Pavao , Berberich Samantha , Dahlquist Maxwell , Evans Sarah , Jain Mayank , Layzell Anthony , Nara Yoshitaka , Rinehart Alex , Sellwood Elaine , Shaanan Uri , Yuan Yang , Morovati Mehdi
Published: October 2023

Rock fracturing drives and limits the evolution of Earth’s topography and life, the global carbon cycle, geologic hazards, and infrastructure stability. Yet there remains a paucity of constraints on long-term fracturing behavior. Here we use field observations to show that fracturing rates in natural surface rocks decrease exponentially over time. We present lab measurements showing that these results are consistent with rock mechanics experimental data and theory linking progressive fracturing to decreasing brittle strain response to stress. We characterize fracture evolution over periods of 1 – 100 kyr for three different field sites and three rock types. For rocks with less than ~5 kyr of exposure, fractures grow at rates on the order of 10 – 100 mm/kyr, then after ~10 – 15 kyr, fractures grow by less than 2 mm/kyr. Over similar timescales, the ‘appearance’ of visible fractures also decreases, dropping from 36 new fractures per m^2/kyr to <2 per m^2/kyr. We independently document similar fracturing deceleration trends using microfracture analyses, plus a novel application of infrared photoluminescence (IRPL) dating for three in situ fractures in a single clast. Our results contrast significantly with current landscape-scale conceptual models that assume fracturing rates and characteristics are invariant over time and are controlled by short term rock strength and external stress magnitudes alone. Instead, our findings indicate that, over geologic time, rock’s fracturing increases its toughness.
Deciphering climate resilience in Indian cattle breeds by selection signature analyses
Authors: Nayak Sonali Sonejita , Panigrahi Manjit , Rajawat Divya , Sharma Anurodh , Jain Karan , Bhushan Bharat , Dutt Triveni
Published: October 2023

The signature of selection is a crucial concept in evolutionary biology that refers to the pattern of genetic variation that arises in a population as a result of natural selection. In climate adaptation, the signature of selection can reveal the genetic basis of adaptive traits that enable organisms to survive and thrive in changing environmental conditions. Breeds cultivated in diverse agroecological zones exhibit genetic "footprints" within their genomes that mirror the influence of climate-induced selective pressures, subsequently impacting phenotypic variance. We examined genotypic data from eight different cattle groups (Gir, Hariana, Kankrej, Nelore, Ongole, Red Sindhi, Sahiwal, and Tharparkar) that are adapted to diverse regional climates in India. It is assumed that the genomes of animals residing in these regions have been altered through selection for various climatic adaptations. In this study, we utilized bovine 50k chip data and four genome scan techniques to assess the genetic regions of positive selection for high-temperature adaptation in eight distinct cattle populations. We have also investigated the population stratification i.e. PCA, genome-wide investigation of genetic diversity, inbreeding, effective population size in our target dataset. To identify selection signature regions in this work, we used four intra-population statistics: Tajima's D, CLR, iHS, and ROH. We identified potential regions for selection that is likely to be caused by climate. We have identified many adaption genes as several potential selection signature areas. These include genes like HSPB2, HSPB3, HSP20, HSP90AB1, HSF4, HSPA1B, CLPB, GAP43, MITF, and MCHR1 that have been previously identified in the cattle population that lives in high- and low-temperature regions.
Evaluation of the Five-item Modified Frailty Index in predicting postoperative complications in lung cancer patients
Authors: Li Dan , Yuan Tingting , Mijiti Maimaiti , Yan Rui
Published: October 2023

Background:
Lung cancer is anticipated to be the most common cancer in China. This study aimed to evaluate the utility of the five-item modified frailty index (mFI-5) as a predictor of postoperative complications in patients undergoing surgery for lung cancer.
Methods:
This retrospective cohort study was conducted in a tertiary hospital between January, 2020, and September, 2021. We included adults with lung cancer undergoing surgery and conducted bivariate statistical analyses using Fisher's exact test, chi-square test, and independent samples t-test. Logistic regression models were used for the multivariate analysis.
Results:
We included 541 patients (37.2% male, 62.8% female; mean age, 57.4 ± 10.4 years) with a prevalence of frailty of 9.06%. The presence of frailty was associated with higher complications according to the Clavien–Dindo classification (odds ratio: 3.88; 95% confidence interval: 1.94 − 7.73). The consistency of the regressions indicates the robustness of the results.
Conclusion:
Our study indicates that the mFI-5 based on data from medical records is a pragmatic tool that can independently predict postoperative complications in patients with lung carcinoma undergoing surgery. Upon further validation, integration of this tool into clinical practice may be beneficial for optimizing patient risk stratification.
Categorization of Disaster-Related Deaths in Minamisoma City after the Fukushima Nuclear Disaster Using Clustering Analysis
Authors: Yoshimura Hiroki , Sawano Toyoaki , Murakami Michio , Uchi Yuna , Kawashima Moe , Kitazawa Kenmei , Nonaka Saori , Ito Naomi , Saito Hiroaki , Abe Toshiki , Moriyama Nobuaki , Sakakibara Mamoru , Yagiuchi Kazuko , Otsuki Mako , Hori Arinobu , Ozaki Akihiko , Yamamoto Chika , Zhao Tianchen , Uchiyama Taiga , Oikawa Tomoyoshi , Niwa Shinichi , Tsubokura Masaharu
Published: October 2023

The medical situation during disasters often differs from that at usual times. Disasters can lead to significant mortality that can be difficult to monitor. The types of disaster-related deaths are largely unknown. In this study, we conducted a survey to categorize the disaster-related deaths caused by a radiation disaster. A total of 520 people living in Minamisoma City, Fukushima Prefecture, at the time of the Fukushima Daiichi Nuclear Power Plant accident, who were certified to have died due to disaster-related causes were surveyed. We divided the participants into those who were at home at the time of the earthquake and those who were in hospitals or facilities when the disaster struck and conducted a hierarchical cluster analysis of the two groups. Disaster-related deaths could be divided into seven groups for those who were at home at the time of the disaster and five groups for those who were in hospitals or facilities at the time of the disaster. Each group showed different characteristics, such as "the group with disabilities," "the group receiving care," and "the group with depression," and it became evident that not only uniform post-disaster support, but support tailored to the characteristics of each group is necessary.
A prospective study to evaluate the contribution of Pediatric Appendicitis Score in the decision process
Authors: Vevaud Kevin , Dallocchio Aymeric , Dumoitier Nathalie , Laspougeas Alban , Labrunie Anaïs , Belgacem¹ Alexis , Fourcade¹ Laurent , quentin ballouhey
Published: October 2023

Background
To predict acute appendicitis (AA) probability in children admitted to the emergency department (ED) with abdominal symptoms according to whether or not they had a previous consultation in primary care (PC).
Methods
From February to June 2021, all children admitted to the ED for acute abdominal pain suggestive of AA were prospectively enrolled and then allocated into three groups: assessed by a PC physician (PG); brought in by their family without a prior consultation (FG); admitted after a PC consultation without having been assessed as such. The main objectives were to compare the risk of AA development using the Pediatric Appendicitis Score (PAS). The secondary objectives were to analyze the PAS and CRP (C-reactive protein) levels according to the duration of pain and the definitive diagnoses.
Results
124 children were enrolled (PG, n = 56; FG, n = 55; NG, n = 13). Twenty-nine patients (23.4%) had AA. Of these, 13 (23.2%) were from the PG and 14 (25.4%) were from the FG. The mean PAS scores for AA cases from the PG and the FG were 6.69 ± 1.75 and 7.57 ± 1.6, respectively, (p = 0.3340). The PAS scores and the CRP levels were significantly correlated to AA severity. There were no AA cases for PAS scores < 4.
Conclusions
There was no difference in the PAS scores between patients addressed by PG and FG even if this score was higher for patients with AA. We propose a new decisional algorithm for PC practice that integrates inflammatory markers and duration of pain.
Trial registration:
Institutional Ethics Committee number registration: 447-2021-103 (10/01/2021)
Virtual Reality Experiential Learning Improved Undergraduate Students’ Knowledge and Evaluation Skills Relating to Assistive Technology for Older Adults and Individuals with Disabilities
Authors: Chen Peng-Hsu , Ho Hsuan-Wei , Chen Hung-Chou , Tam Ka-Wai , Liu Ju-Chi , Lin Li-Fong
Published: October 2023

Background: The aging population has caused assistive technology (AT) to receive attention. Thus, ensuring accurate user comprehension of AT has become increasingly crucial, and more specialized education for students in relevant fields is necessary. On the basis of the success of virtual reality (VR) education in multiple areas, this experiment investigated the impact of using head-mounted display–immersive virtual reality (HMD-IVR)technology to teach AT-related knowledge and evaluation skills to undergraduate students on the basis of experiential learning theory.
Methods: A parallel-group design was used. Sixty third-year university students studying gerontology and long-term-care-related subjects in Taiwan were enrolled, with the experimental (VR) and control (two-dimensional [2D] video) groups each comprising 30 participants.Both groups received the same 15-minute lecture. Subsequently, the experimental group received experiential learning through a VR intervention, whereas the control group watched a 2D video to learn. The students’ knowledge of AT was assessed using a pretest and posttest. Additionally, their skills in evaluation of residential environments were assessed using the Residential Environment Assessment (REA) Form for Older Adults. All data analyses were performed with SPSS version 22.
Results: In the posttest conducted after the intervention, the experimental group exhibited a significant 20.67 point improvement (p < 0.05), whereas the control group only exhibited improvement of 3.67 points (p= 0.317). Furthermore, the experimental group demonstrated a significantly higher score (+2.17 points) on the REA Form for Older Adults than did the control group (p < 0.05).
Conclusion: The use of VR experiential learning can significantly improve undergraduate students’ knowledge and evaluation skills in relation to AT for older adults and individuals with disabilities.
Serotonin Reuptake Inhibition for the Prevention of Vasovagal Syncope: A Systematic Review and Meta-Analysis
Authors: Raj Priya , Lei Lucy , Flevaris Panagiota , Raj Satish , Sheldon Robert S.
Published: October 2023

Purpose: Vasovagal syncope is a common clinical condition that lacks effective medical therapies despite being associated with significant morbidity. Current guidelines suggest that serotonin-specific reuptake inhibitors, might suppress vasovagal syncope but supporting studies have been small and heterogenous. The purpose was to evaluate the efficacy of serotonin-specific reuptake inhibitors to prevent syncope in patients with recurrent vasovagal syncope by conducting a systematic review and meta-analysis of published studies.
Methods: Relevant randomized controlled trials were identified from the MEDLINE and Embase databases without language restriction from inception to August 2022, and clinicaltrials.gov. All studies were conducted in clinical syncope populations and compared the benefit of serotonin versus placebo. Weighted relative risks were estimated using random effects meta-analysis techniques.
Results: Three studies (n=204) met inclusion criteria. Patients were 42±13 years of age and 51% female. Serotonin-specific reuptake inhibitors were found to substantially reduce the likelihood of a patient having at least one recurrence of vasovagal syncope (relative risk [RR]=0.34 (0.20-0.60), p<0.01) with minimal between-study heterogeneity (I2=0%, p = 0.67). Serotonin-specific reuptake inhibitors in two reports provided significant protection against clinical presyncope (RR = 0.43 (0.24-0.77, p <0.01), with minimal between-study heterogeneity (I2 = 0%, p = 0.80).
Conclusions: Serotonin-specific reuptake inhibitors may be effective in preventing syncope induced by head-up-tilt testing and in syncope in the community in randomized, double-blinded clinical trials.
Genotoxic Effects of Iprodione and Tebuconazole on Allium cepa meristem cells: concentration and time-dependent responses and implications for hazard assessment
Authors: Mendoza Grace Stephany Solano , Andrioli Nancy Beatriz
Published: October 2023

The present work explores the genotoxicity of fungicides Iprodione (IP) and Tebuconazole (TB) using the Allium cepa assay as in vivo biological model. Both short-term and long-term exposures were studied, revealing concentration-dependent cytological and genotoxic effects. IP exhibited genotoxicity over a wider concentration range (5–50 µg/ml) and required longer exposure, while TB showed more genotoxicity at higher concentrations and shorter exposure times. The study highlights the importance of assessing potential risks associated with fungicide exposure, including handling, disposal, and food residue concerns. The research underscores the genotoxic effects of IP and TB on plant cells and provides valuable insights into their concentration and time-response patterns.
Mode of Progression in Smoldering Multiple Myeloma: A study of 406 patients
Authors: Rajkumar S , Abdallah Nadine , Lakshman Arjun , Kumar Shaji , Cook Joselle , Binder Moritz , Kapoor Prashant , Dispenzieri Angela , Gertz Morie , Lacy Martha , HAYMAN Suzanne , Buadi Francis , Dingli David , Lin Yi , Kourelis Taxiarchis , Warsame Rahma , Bergsagel P. Leif
Published: October 2023

The approach to patients with high-risk smoldering multiple myeloma (SMM) varies among clinicians; while some advocate early intervention, others reserve treatment at progression to multiple myeloma (MM). We aimed to describe the myeloma-defining events (MDEs) and clinical presentations leading to MM diagnosis among SMM patients seen at our institution. We included 406 patients diagnosed with SMM between 2013-2022, seen at Mayo Clinic, Rochester, MN. The 2018 Mayo 20/2/20 criteria were used for risk stratification. Median follow-up was 3.9 years. Among high-risk patients who did not receive treatment in the SMM phase (n=71), 51 progressed by last follow-up; the MDEs included: bone lesions(37%), anemia(35%), hypercalcemia(8%), and renal failure(6%); 24% met MM criteria based on marrow plasmacytosis (≥60%) and/or free light chain ratio (>100); 45% had clinically significant MDEs (hypercalcemia, renal insufficiency, and/or bone lesions). MM diagnosis was made based on surveillance labs/imaging(45%), testing obtained due to provider suspicion for progression(14%), bone pain(20%), and hospitalization/ED presentations due to MM complications/symptoms(4%). The presentation was undocumented in 14%. A high proportion (45%) of patients with high-risk SMM on active surveillance develop end-organ damage at progression. About a quarter of patients who progress to MM are not diagnosed based on routine interval surveillance testing.
Altitude and polarity transitions of corona activity in thundercloud tops reaching the lower stratosphere
Authors: Lei Jiuhou , Liu Feifan , Neubert Torsten , Chanrion Olivier , Lu Gaopeng , Wu Ting , Lyu Fanchao , Lyu Weitao , Köhn Christoph , Li Dongshuai , Zhu Baoyou
Published: October 2023

Thunderclouds occasionally penetrate into the stratosphere, forcing the exchange of air masses between the troposphere and the stratosphere. Observations from space have shown that blue corona discharges are often generated in such thundercloud tops and are the optical manifestation of so-called Narrow Bipolar Events (NBEs) observed in radio signals. They come with two polarities, the positive that brings net negative charge aloft, and the negative that brings negative charge towards the earth. While their production appears to depend on convection, the cause and nature of such discharges are not well known. Here we report the observations by a lightning detection array of unusual amounts of NBEs during a tropical storm on the coastline of China. NBEs of negative polarity are predominantly observed at the top of the cloud reaching the tropopause and into the stratosphere, and positive NBEs are primarily at lower altitudes. We find that either positive or negative polarities dominate at a time, shifting between the two with a ~30 min period. The period is close to the typical time of development of thunderstorm cells, suggesting that the polarity depends on the phase of the storm cell. Furthermore, we find that the lightning jump of negative NBEs is associated with the occurrence of above-anvil cirrus plumes (AACPs) of ice crystals and water vapor in the lower stratosphere resulting from the strong updraft. We propose that variations in updrafts induce changes in the altitude and charge concentrations of the cloud layers, which lead to the polarity transition. Our results have implications for studies of the chemical perturbations of greenhouse gas concentrations at the tropopause by corona discharges at the tropopause.
GPIP: Geometry-enhanced Pre-training on Interatomic Potentials
Authors: Su Mao , Zhang Shufei , Cui Taoyong , Tang Chenyu , Li Yuqiang , Dong Yuhan , Gong Xingao , Ouyang Wanli , Bai Lei
Published: October 2023

Machine learning interatomic potentials (MLIPs) enables molecular dynamics (MD) simulations with ab initio accuracy and has been applied to various fields of physical science. However, the performance and transferability of MLIPs are limited by insufficient labeled training data, which require expensive ab initio calculations to obtain the labels, especially for complex molecular systems. To address this challenge, we design a novel geometric structure learning paradigm that consists of two stages. We first generate a large quantity of 3D configurations of target molecular system with classical molecular dynamics simulations. Then, we propose geometry-enhanced self-supervised learning consisting of masking, denoising, and contrastive learning to better capture the topology and 3D geometric information from the unlabeled 3D configurations. We evaluate our method on various benchmarks ranging from small molecule datasets to complex periodic molecular systems with more types of elements. The experimental results show that the proposed pre-training method can greatly enhance the accuracy of MLIPs with few extra computational costs and works well with different invariant or equivariant graph neural network architectures. Our method improves the generalization capability of MLIPs and helps to realize accurate MD simulations for complex molecular systems.
Cholangiocyte Organoids to Model Chlorpromazine-Induced Bile Duct Injury
Authors: Wang Zhenguo , Xing Chen , Laan Luc J.W. van der , Verstegen Monique M.A. , Spee Bart , Masereeuw Rosalinde
Published: October 2023

Background Drug induced bile duct injury is a frequently observed clinical problem leading to a wide range of pathological features. During the past decades, several agents have been identified with various postulated mechanisms of bile duct damage, however, mostly still poorly understood.
Methods Here, we investigated the mechanisms of chlorpromazine(CPZ) induced bile duct injury using advanced in vitro cholangiocyte cultures. Intrahepatic cholangiocyte organoids (ICOs) were driven into mature cholangiocyte like cells (CLCs), which were exposed to CPZ under cholestatic or non-cholestatic conditions through the addition of a bile acid cocktail.
Results CPZ caused loss of monolayer integrity by reducing expression levels of tight junction protein 1 (TJP1), E-cadherin 1 (CDH1) and lysyl oxidase homolog 2 (LOXL2). Loss of zonula occuludens-1 (ZO-1) and E-cadherin was confirmed by immunostaining after exposure to CPZ and rhodamine-123 leakage further confirmed disruption of the cholangiocyte barrier function. Furthermore, oxidative stress seemed to play a major role in the early damage response by CPZ. The drug also decreased expression of three main basolateral bile acid transporters, ABCC3 (ATP binding cassette subfamily C member 3), SLC51A/B (solute carrier family 51 subunit alpha/beta) and multidrug resistance transporter ABCB1 (ATP binding cassette subfamily B member 1), thereby contributing to bile acid accumulation. CPZ did not induce an inflammatory response by itself, but addition of TNFα revealed a synergistic effect.
Conclusion These results show that ICOs present a model to identify toxic drugs affecting the bile ducts while providing mechanistic insights into hepatotoxicity.
Intra-articular injection of stigmasterol loaded nanoparticles is effective in inhibiting joints destruction in an osteoarthritis rat model
Authors: Lim Ji Hyun , Kim Sung Eun , Kim Hak-Jun , Song Gwan Gyu , Jung Jae Hyun
Published: October 2023

Stigmasterol, a plant-derived sterol, sharing structural similarity with cholesterol, has demonstrated anti-osteoarthritis (OA) properties, attributed to its antioxidant and anti-inflammatory capabilities. Given that OA often arises in weight bearing or overused joints, prolonged localized treatment effectively targets inflammatory aspects of the disease. This research explored the impact of stigmasterol-loaded nanoparticles delivered via intra-articular injections in an OA rat model. Employing mesoporous silica nanomaterials (MSNs) combined with β-cyclodextrin (β-CD) as a vehicle, stigmasterol was loaded in conjunction with tannic acid, forming stigmasterol/β-CD-MSNs to facilitate a sustained stigmasterol release. The study employed RAW 264.7 cells to examine the in vitro cytotoxicity and anti-inflammatory effect of stigmasterol/β-CD-MSNs. For in vivo experimentation, we used healthy control rats and monosodium iodoacetate (MIA)-induced OA rats, separated into five groups, varying the injection substances. In vitro findings indicated that stigmasterol/β-CD-MSNs suppressed the mRNA expression of key pro-inflammatory mediators such as interleukin-6, tumor necrosis factor-α, and matrix metalloproteinase-3 in a dose-dependent manner. In vivo experiments revealed a substantial decrease in the mRNA levels of pro-inflammatory factors in the stigmasterol(50 µg)/β-CD-MSN group compared to the others. Macroscopic, radiographic, and histological evaluations established that intra-articular injections of stigmasterol/β-CD-MSNs inhibited cartilage degeneration and subchondral bone deterioration. Therefore, in a chemically induced OA rat model, intra-articular stigmasterol delivery was associated with reduction in both local and systemic inflammatory responses, alongside a slowdown in joint degradation and arthritic progression.
Machine learning-based prediction model for neurodegenerative disease in patients with type 2 diabetes: derivation and validation in two independent Korean cohorts
Authors: Rhee Sang Youl , Sang Hyunji , Lee Myeongcheol , Lee Hojae , Park Jaeyu , Kim Sunyoung , Woo Ho Geol , Koyanagi Ai , Smith Lee , Lee Sihoon , Hwang You-Cheol , Park Tae Sun , Lim Hyunjung , Yon Dong Keon
Published: October 2023

Background Several machine learning (ML) prediction models for neurodegenerative diseases (ND) in type 2 diabetes mellitus (T2DM) have recently been developed. However, the predictive power of these models is limited by the lack of multiple risk factors. This study aimed to assess the validity and utility of an ML model for predicting the three year incidence of ND in patients with T2DM.Methods We used data from two independent cohorts, the discovery cohort (one hospital; n = 22,311) and the validation cohort (two hospitals; n = 2,915), to predict ND. The outcome of interest was the presence or absence of ND at three years. We selected different ML-based models with hyperparameter tuning in the discovery cohort and conducted an area under the receiver operating characteristic curve (AUROC) analysis in the validation cohort.Results The study dataset included 22,311 (discovery) and 2,915 (validation) patients with T2DM recruited between 2008 and 2022. ND was observed in 133 (0.6%) and 15 patients (0.5%) in the discovery and validation cohorts, respectively. The AdaBoost model had a mean AUROC of 0.82 (95% CI, 0.79–0.85) in the discovery dataset. When this result was applied to the validation dataset, the AdaBoost model exhibited the best performance among the models, with an AUROC of 0.83 (accuracy of 78.6%, sensitivity of 78.6%, specificity of 78.6%, and balanced accuracy of 78.6%). The most influential factors in the AdaBoost model were age and cardiovascular disease.Conclusions This study shows the utility and feasibility of ML for assessing the incidence of ND in patients with T2DM and suggests its potential for use in screening patients. Further international studies are required to validate these findings.
Emergency department visits for dog bite injuries in Missouri municipalities with and without Breed-Specific Legislation: a propensity score-matched analysis
Authors: Wyker Brett , Gupta Maya
Published: October 2023

Background
Breed-Specific Legislation is a type of law that bans or restricts ownership of specific dog breeds. Some local governments – including over seventy municipalities in the state of Missouri - have enacted Breed-Specific Legislation to prevent injuries from dog bites. Several studies from the peer-reviewed literature have found that aggressive behavior is not associated with any particular dog breeds and, since 2018, at least a dozen municipalities in Missouri have repealed these laws. To evaluate the impact of Breed-Specific Legislation on public safety, the 2010-2015 rates of emergency department visits for dog bite-related injuries in Missouri municipalities with and without Breed-Specific Legislation were compared. Propensity-score matched linear regression models were used to assess the effect of breed restrictions on injury rates while balancing the samples on population characteristics and estimates of dog ownership.
Findings
After matching the sample on population, housing and dog ownership estimates, no association was found between emergency department visits for dog bite injuries and whether the municipality enacted Breed-Specific Legislation. However, with every 1% increase in the population of males aged 5 to 9 the rate of emergency room visits for dog bite-related injuries increased by 6.36 visits per 100,000 residents (p<0.01.)
Conclusion
This study has found breed discriminatory laws have not reduced the risk of emergency department visits for injury from dog bites in Missouri. There appears to be no greater risk to public safety as local governments move to repeal existing breed bans.
June 2023 marine heatwave over the Northwest European shelf: origins, weather feedback and future recurrence
Authors: Berthou Ségolène , Renshaw Richard , Smyth Tim , Tinker Jonathan , Grist Jeremy , Wihsgott Juliane , Jones Sam , Inall Mark , Nolan Glenn , Arnold Alex , Castillo Juan Manuel , Blunn Lewis , Gomez Breogan , Leonhardt Vivian Fraser , Hirschi Joel J-M , Lewis Huw , Mahmood Sana , Worsford Mark
Published: October 2023

The Northwest European shelf (NWS) experienced its longest recorded category II marine heatwave (MHW) in June 2023 (16 days). Locally, it reached category IV north of Ireland (anomalies up to 5 °C). With state-of-the-art observation and modelling capabilities, we show the MHW developed quickly in the first half of June due to strong atmospheric forcing (high level of sunshine, weak winds and waves, tropical air) during neap tides. This shallow MHW then maintained itself by reducing cloud cover in persistent anticyclonic conditions, followed by another week of neap tides. The MHW impacted the weather of northern Europe with stronger, warmer and moister sea breezes generating more rainfall and contributing to the breaking of June mean temperature records. This MHW was additional to climatological sea surface temperatures +0.9 °C warmer over the last 20 years. These MHW temperatures are projected to become commonplace by the middle of the century under a high CO2 emission scenario.
Structural Basis of Directional Switching by the Bacterial Flagellum
Authors: Lea Susan , Johnson Steven , Deme Justin , Furlong Emily , Chevance Fabienne , Hughes Kelly , Caesar Joseph
Published: October 2023

The bacterial flagellum is a macromolecular protein complex that harvests energy from ion-flow across the inner membrane to power bacterial swimming in viscous fluids via rotation of the flagellar filament. Bacteria such as Salmonella enterica are capable of bi-directional flagellar rotation even though ion flow is uni-directional. How uni-directional ion-movement through the inner membrane is utilized by this macromolecular machine to drive bi-directional flagellar rotation is not understood, but a chemotactic response regulator in the cytoplasm is known to reverse the direction of rotation. We here present cryo-EM structures of intact Salmonella flagellar basal bodies, including the cytoplasmic complexes required for power transmission, in conformations representing both directions of rotation. The structures reveal that the conformational changes required for switching the direction of rotation involve 180 degree rotations of both the N- and C-terminal domains of the FliG protein. Combining these models with a new, high-resolution, cryo-EM structure of the MotA5B2 stator, in complex with the C-terminal domain of FliG, reveals how uni-directional ion-flow across the inner membrane is used to accomplish bi-directional rotation of the flagellum.
Space-time autoregressive Hilbertian models andtheir application for wind speed
Authors: Hashemi Maryam , Zamani Atefeh , Nasirzadeh Roya
Published: October 2023

We propose a novel approach for space-time functional data analysis based on aspace-time autoregressive Hilbertian model. This model can capture the dynamicand spatial dependence of functional data over time and space. We provide suf-ﬁcient conditions for the existence and uniqueness of the model and establish itsasymptotic properties, such as the strong law of large numbers and the centrallimit theorem. We also develop a consistent estimator for the model parametersand evaluate its performance through simulations and a real data example onwind speed data.
Evaluating the Effectiveness of Positive psychology intervention to improve mental wellbeing among Bereaved Families
Authors: Aslam Mehreen , Tharani Ambreen , Parpio Yasmin Nadeem , Jan Rafat
Published: October 2023

Introduction One of the most traumatic experiences a person can have is losing a loved one, which may substantially affect their physical, socioeconomic, and emotional health. According to the World Health Organization (2017), approximately 300 million people are suffering from mental health problems due to traumatic experiences. Purpose: The current study will provide insight into how to improve the social, emotional, and psychological well-being of bereaved families, which will ultimately result in their mental well-being. The purpose of the current study is to determine whether six weeks of positive psychology intervention, comprising, mindfulness, spirituality, physical activity, happiness, gratitude, and social support can assist in enhancing mental health. Methods A quasi-experimental Study on the females of bereaved families (18 years and above, wife, mother, daughters, and sisters) living within premises of Karachi, (Sindh), Pakistan. The non-probability (consecutive sampling) will be used to select the study participants. The participants will be divided into two groups. Data will be collected from the wait list control group participants during the May 2023 –June 2023 baseline and only a booklet of self-care strategies will be given to all participants and post-intervention after 6 weeks (T2) and 12 weeks (T3) and they will receive intervention in 6 sessions after the completion of the study. From July 2023 – August 2013, data will be collected from the intervention group participants at (T1) pre-intervention then intervention will be given in 6 sessions, and then at the end of intervention (T2) 6 weeks and after 12th weeks (T3). The acceptability, and applicability of this intervention will also be assessed quantitatively via a questionnaire on a 1 to 4 Likert scale Dissemination The perceived stress of losing a loved one affects family members' health and well-being. The development of a positive psychology-based training module and testing its efficacy and feasibility to improve the mental well-being and life satisfaction of bereaved families. Moreover, opportunities to interact with people of the same background will enable women to develop coping strategies to deal with the stresses and enhance their subjective well-being. This study will considerably contribute to the global body of knowledge on the effectiveness of positive psychology interventions as a viable method for managing the psychological repercussions of sudden bereavement in low-resource settings Conclusions: Results will assist the work of researchers, clinicians, and policymakers to support the implementation of effective practices and improve the quality of services for bereaved families.
Dapagliflozin alleviates high-fat-induced obesity cardiomyopathy by inhibiting ferroptosis
Authors: Chen Di , Shi Jiahao , Xuan Tianluo , Wang Yixuan , Wang Zilin , Xu Siwei , Jiang Shasha
Published: October 2023

Dapagliflozin (Dapa), a selective sodium-glucose cotransporter 2 inhibitor, not only has a stable hypoglycemic function but also exerts a protective effect in cardiovascular diseases. The present study aimed to investigate whether Dapa could effectively protect high-fat diet (HFD)-induced obesity-related cardiomyocytes and its mechanism. Rats were fed with a HFD for 16 weeks and the obesity cardiomyopathy was confirmed by testing of metabolic parameters. The results demonstrated that Dapa treatment led to more obvious weight loss and a lower Lee’s index. Furthermore, Dapa administration reduced the lipid levels, including total cholesterol and low-density lipoprotein cholesterol levels, and improved the insulin sensitivity/resistance index, whereas the blood pressure was not markedly different after Dapa intervention. Echocardiography and histological analysis revealed that Dapa could effectively alleviate obesity-induced the myofibrils dissolved, collagen deposition and mitochondrial damage, and finally improved the heart function and cardiac remodeling. The present study also emphasized the vital role of Dapa in the protection obesity-related cardiac dysfunction and cardiac remodeling by inhibiting ferroptosis. Dapa treatment ameliorated the ferroptosis-related changes by attenuating iron ion deposition and decreased over-activation of the key factors of ferroptosis, including glutathione peroxidase 4, solute carrier family 7 member 11, transferrin 1 and ferritin heavy chain 1, in cardiomyocytes. In conclusion, Dapa exerted a direct protective effect against obesity cardiomyopathy by inhibiting ferroptosis.
ZNT1 involves cuproptosis through regulating MTF1-conduced expression of MT1X under copper overload
Authors: Wu Yue , Yang Tingyun , Yan Bo , Ai Youwei , Chen Fang , Ma Juan , Liu Sijin
Published: October 2023

Background
Copper is an essential but also toxic heavy metal. As a crucial micronutrient, copper is required for various enzymes in physiology and pathology. Meanwhile, copper overload has currently raised serious public health concerns. Copper overload can perturb intracellular homeostasis and induce oxidative stress and even cell death. More recently, cuproptosis has been identified as a copper-dependent form of cell death induced by oxidative stress in mitochondria. This mitochondrial cell death is characterized by lipoylated protein aggregation and loss of iron-sulfur cluster proteins. However, the current comprehension of the mechanisms underlying copper toxicity remains relatively limited, particularly concerning the molecular regulatory mechanism against cuproptosis.
Methods
We constructed HeLa-Cas9-SLC31A1 cells for Genome-wide CRISPR/Cas9 screen to identify new components in the execution of cuproptosis. Also, we established single and double knock out models to examine the influence of candidate genes– zinc transporter 1 (ZNT1) and metal-response element-binding transcription factor-1 (MTF1) on the accumulation of cellular copper. Additionally, we performed metallothionein 1X (MT1X) overexpression and zinc/copper competitive combination experiments to explore their functions in cuproptosis. This regulatory effect was further verified in a mouse model with copper-dependent liver injury.
Results
We uncover here that ZNT1 is an important regulator involved in cuproptosis. Mechanistically, because zinc is a direct activator of MTF1, knockout of ZNT1 enhanced intracellular zinc levels and then promoted MT1X expression by strongly driving MTF1 transcription factor. As a consequence, the interaction between MT1X and copper was strengthened, reducing the flow of copper into mitochondria and eliminating mitochondria damages.
Conclusions
This study reveals the important role of ZNT1 in cuproptosis and shows MTF1-MT1X axis mediated resistance to cuproptosis. Moreover, our study will help to understand the regulatory mechanism of cellular and systemic copper homeostasis under copper overload, and present novel insights into novel treatments for damages caused by both genetic copper overload diseases and environmental copper contamination.