bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid SERS substrate based on cotton swab for sensitive detection of organic molecules
Authors: Minh Hoang Duy , Thang Nguyen Duc , Chi Nguyen Thao Linh , Anh Luong Duc , Long Le Ngoc , Van Khai Tran , Khanh Huynh Cong , Khoa Nguyen Dang , Minh Tran Hoang
Published: December 2023

For the last two decades, the development of substrates for Surface Enhanced Raman Spectroscopy (SERS) has been continuously pushed for better performances. In this research, we designed SERS substrates with better detection capability and more efficient sample collection. In particular, morphology-controlled Ag nanoparticles were deposited onto cotton swab (cotton Q-tip), followed by a thin cover layer of graphene oxide by the dip-coating method. The graphene oxide overlay was expected to not only protect Ag nanoparticles from degradation by the environment but also contribute to sample adsorption and signal enhancement. To demonstrate the performance of the SERS substrates, different concentrations of Rhodamine B as low as 10–10 M were successfully detected and the enhancement factors were estimated to be 3 × 1010–5 × 1010. It is our expectation that these cotton swab-based substrates will contribute to our ongoing efforts toward low-cost, high-efficiency and durable SERS substrate.
Electrodeposited Ni-Sn-P electrodes for hydrogen evolution electrocatalysis
Authors: Zhou Yanke , Zhang Zhaoyu , Sun Hebin
Published: December 2023

Developing high-activity, Nobel metal-free electrodes is of utmost significance in the context of the hydrogen evolution reaction (HER). In this study, we employed an electrodeposited process to fabricate Ni-Sn-P films on a copper substrate. The microstructure and electrocatalytic properties of these Ni-Sn-P films were thoroughly characterized and subsequently compared to those of the reference Ni-P films.Remarkably, the Ni-Sn-P electrode exhibited an impressively low overpotential of −84 mV at a current density of −10 mA cm−2 in a 1 M NaOH solution. This value was found to be 172 mV lower than that of the Ni-P electrode, thereby establishing the superior electrocatalytic activity of the Ni-Sn-P electrode. Moreover, the excellent electrocatalytic stability of the Ni-Sn-P electrode was demonstrated over a time span of at least 25 h.The exceptional attributes of the Ni-Sn-P electrode can be ascribed to its larger active surface area, lower Tafel slope, and reduced charge transfer resistance. The utilization of Ni-Sn-P films as electrode materials holds great potential in advancing the field of HER due to their enhanced performance compared to conventional Ni-P films.
Sarah Polley’s take on the Me Too moment: adapting Women Talking to the big screen
Authors: Fernández-Morales Marta , Menéndez-Ménendez María Isabel
Published: December 2023

This article discusses Sarah Polley’s 2022 film adaptation of Miriam Toews’ novel Women Talking (2018), inspired by a case of mass rapes in a Mennonite colony in Bolivia, as part of the Me Too moment; a new zeitgeist that has modified the conditions of reception for survivor testimony. We examine it as an audiovisual product that amplifies the resonance of the original text and contributes to the current wave of feminist testimonial practices about sexual violence, constituting an instance of narrative activism that promotes social change. Through our analysis of the dynamics of storytelling in the film, we prove that Polley’s cinematic strategies place emphasis on the women’s lived experiences and points of view, distilling the words of the book to capture the key elements of their discussion (forgiveness, justice, obedience, trauma, and structural violence) and, rarely but significantly, deviating from the original text to achieve her goal of female-centred focalisation. While scholars and survivors have described the battle over the narrative in rape cases, Polley does not leave room for it. In line with #MeToo, the movie takes an ethical listening stand, presenting female testimony as valid evidence. The question at stake is not whether the protagonists have been raped by the men of the colony, but what they are going to do about it; and, by extension, what the viewers are going to make of their story as told by themselves.
ESQmodel: biologically informed evaluation of 2-D cell segmentation quality in multiplexed tissue images
Authors: Lee Eric , Lee Dongkyu , Fan Wayne , Lytle Andrew , Fu Yuxiang ,   IMAXT Consortium, Scott David W , Steidl Christian , Aparicio Samuel , Roth Andrew
Published: December 2023

Motivation

Single cell segmentation is critical in the processing of spatial omics data to accurately perform cell type identification and analyze spatial expression patterns. Segmentation methods often rely on semi-supervised annotation or labeled training data which are highly dependent on user expertise. To ensure the quality of segmentation, current evaluation strategies quantify accuracy by assessing cellular masks or through iterative inspection by pathologists. While these strategies each address either the statistical or biological aspects of segmentation, there lacks a unified approach to evaluating segmentation accuracy.

Results

In this article, we present ESQmodel, a Bayesian probabilistic method to evaluate single cell segmentation using expression data. By using the extracted cellular data from segmentation and a prior belief of cellular composition as input, ESQmodel computes per cell entropy to assess segmentation quality by how consistent cellular expression profiles match with cell type expectations.

Availability and implementation

Source code is available on Github at: https://github.com/Roth-Lab/ESQmodel.
Regional assessment of availability for transcatheter aortic valve implantation in Sweden: a long-term observational study
Authors: Nilsson Konrad , Lindholm Daniel , Backes Jenny , Bjursten Henrik , Hagström Henrik , Lindbäck Johan , Pétursson Pétur , Settergren Magnus , Sarno Giovanna , James Stefan
Published: December 2023

Background

Transcatheter aortic valve implantation (TAVI) is an increasingly important treatment option for patients with severe aortic stenosis. Its best implementation is debated, as few centres with high volumes are associated with better outcomes, while centralization might lead to an inferior availability of treatment for patients living far away. The aim of this study was to investigate the implementation of TAVI in Sweden with a focus on regional differences in terms of availability, short-term mortality, and waiting times.

Methods

All patients undergoing TAVI between 2008 and 2020 from the Swedish Transcatheter Cardiac Intervention Registry (SWENTRY) were included. SWENTRY was linked to the National Cause of Death Registry and to publicly available geospatial data from Statistics Sweden.

Results

A total of 7280 patients were included. Over time, TAVI interventions increased markedly, while surgical aortic valve replacement (SAVR) remained constant. There were no statistically significant regional differences in incidence between counties with or without a local TAVI centre (P = 0.7) and no clustering tendencies around regions with a local TAVI centre (P = 0.99). Thirty-day mortality improved over time without evidence of regional differences. No regional differences in waiting time from decision to intervention were found for TAVI centre regions and non-TAVI centre regions (P = 0.7).

Conclusion

This nationwide study indicated no regional differences in terms of availability, short-term mortality, or waiting times. An organization with a few specialized centres was found to be sufficient to provide national coverage of TAVI interventions.
Taking Back Control? Quasi-Experimental Evidence on the Impact of Retirement on Locus of Control
Authors: Clark Andrew E , Zhu Rong
Published: December 2023

We use Australian panel data to examine the impact of retirement on individual locus of control, a socio-emotional skill with substantial explanatory power for a broad range of life outcomes. Exploiting the eligibility age for the Australian Age Pension, we find that retirement leads to increased internal locus of control. This greater internal control explains around one-third and one-fifth of the positive effects of retirement on health and subjective well-being, respectively. We also show that locus of control is much more malleable at retirement than the other socio-emotional skills of the Big-Five personality traits, risk and time preferences, and trust.
Association between mucosectomy and endoscopic outcomes in patients with ileal pouch–anal anastomosis
Authors: Hembree Amy , Shen Bo , Freedberg Daniel
Published: December 2023

Background

In patients with inflammatory bowel disease (IBD) for whom medical therapy is unsuccessful or who develop colitis-associated neoplasia, restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) is often indicated. One consideration for surgeons performing this procedure is whether to create this anastomosis using a stapled technique without mucosectomy or using a hand-sewn technique with mucosectomy. This study tested the association between IPAA anastomosis technique and cuffitis and/or pouchitis, assessed endoscopically.

Methods

This was a retrospective cohort study. We included consecutive adult patients with IBD who had undergone IPAA and had received index pouchoscopies at Columbia University Irving Medical Center between 2020 and 2022. Patients were then followed up from this index pouchoscopy for ≤12 months to a subsequent pouchoscopy. The primary exposure was mucosectomy vs non-mucosectomy and the primary outcome was cuffitis and/or pouchitis, defined as a Pouch Disease Activity Index endoscopy subscore of ≥1.

Results

There were 76 patients who met study criteria including 49 (64%) who had undergone mucosectomy and 27 (36%) who had not. Rates of cuffitis and/or pouchitis were 49% among those with mucosectomy vs 41% among those without mucosectomy (P = 0.49). Time-to-event analysis affirmed these findings (log-rank P = 0.77). Stricture formation was more likely among patients with mucosectomy compared with those without mucosectomy (45% vs 19%, P = 0.02).

Conclusions

There was no association between anastomosis technique and cuffitis and/or pouchitis among patients with IBD. These results may support the selection of stapled anastomosis over hand-sewn anastomosis with mucosectomy.
Phased genomics reveals hidden somatic mutations and provides insight into fruit development in sweet orange
Authors: Wang Nan , Chen Peng , Xu Yuanyuan , Guo Lingxia , Li Xianxin , Yi Hualin , Larkin Robert M , Zhou Yongfeng , Deng Xiuxin , Xu Qiang
Published: December 2023

Although revisiting the discoveries and implications of genetic variations using phased genomics is critical, such efforts are still lacking. Somatic mutations represent a crucial source of genetic diversity for breeding and are especially remarkable in heterozygous perennial and asexual crops. In this study, we focused on a diploid sweet orange (Citrus sinensis) and constructed a haplotype-resolved genome using high fidelity (HiFi) reads, which revealed 10.6% new sequences. Based on the phased genome, we elucidate significant genetic admixtures and haplotype differences. We developed a somatic detection strategy that reveals hidden somatic mutations overlooked in a single reference genome. We generated a phased somatic variation map by combining high-depth whole-genome sequencing (WGS) data from 87 sweet orange somatic varieties. Notably, we found twice as many somatic mutations relative to a single reference genome. Using these hidden somatic mutations, we separated sweet oranges into seven major clades and provide insight into unprecedented genetic mosaicism and strong positive selection. Furthermore, these phased genomics data indicate that genomic heterozygous variations contribute to allele-specific expression during fruit development. By integrating allelic expression differences and somatic mutations, we identified a somatic mutation that induces increases in fruit size. Applications of phased genomics will lead to powerful approaches for discovering genetic variations and uncovering their effects in highly heterozygous plants. Our data provide insight into the hidden somatic mutation landscape in the sweet orange genome, which will facilitate citrus breeding.
Lskipk Lsatpase double mutants are necessary and sufficient for the compact plant architecture of butterhead lettuce
Authors: Xie Sai , Luo Guangbao , An Guanghui , Wang Bincai , Kuang Hanhui , Wang Xin
Published: December 2023

Lettuce, an important leafy vegetable crop worldwide, has rich variations in plant architecture. Butterhead lettuce, a popular horticultural type, has a unique plant architecture with loose leafy heads. The genetic and molecular mechanisms for such a compact plant architecture remain unclear. In this study we constructed a segregating population through crossing a butterhead cultivar and a stem lettuce cultivar. Genetic analysis identified the LsKIPK gene, which encodes a kinase, as the candidate gene controlling butterhead plant architecture. The Lskipk gene in the butterhead parent had a nonsense mutation, leading to a partial predicted protein. CRISPR/Cas9 and complementation tests verified its functions in plant architecture. We showed that the loss of function of LsKIPK is necessary but not sufficient for the butterhead plant architecture. To identify additional genes required for butterhead lettuce, we crossed a butterhead cultivar and a crisphead cultivar, both with the mutated Lskipk gene. Genetic mapping identified a new gene encoding an ATPase contributing to butterhead plant architecture. Knockout and complementation tests showed that loss of function of LsATPase is also required for the development of butterhead plant architecture. The Lskipk Lsatpase double mutation could reduce leaf size and leaf angle, leading to butterhead plant architecture. Expression and cytology analysis indicated that the loss of function of LsKIPK and LsATPase contributed to butterhead plant architecture by regulating cell wall development, a regulatory mechanism different from that for crisphead. This study provides new gene resources and theory for the breeding of the crop ideotype.
Epidemiology of ventilator-associated tracheobronchitis and ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria at a tertiary care hospital in Thailand
Authors: Kajeekul Rattagarn , Thamlikitkul Visanu , Wonglaksanapimon Suvimon , Rattanaumpawan Pinyo
Published: December 2023

Objectives

To investigate the epidemiology of MDR Gram-negative bacilli ventilator-associated tracheobronchitis (MDR GNB-VAT) and MDR GNB ventilator-associated pneumonia (MDR GNB-VAP) among mechanically ventilated patients.

Methods

We conducted a retrospective observational study among hospitalized patients who underwent continuous mechanical ventilation for ≥48 h at Siriraj Hospital, Thailand.

Results

During the 18 month study period, 1824 unique patients underwent continuous mechanical ventilation (12 216 ventilator-days). The cumulative incidences of MDR GNB-VAT and -VAP were 8.4% and 8.3%, respectively. The incidence rates of MDR GNB-VAT and -VAP were 12.52 and 12.44 episodes/1000 ventilator-days, respectively. Among those with VAT, the cumulative incidence and incidence rate of subsequent VAP development within 7 days were 11.76% and 2.81 episodes/1000 ventilator-days, respectively. The median durations of mechanical ventilation before having VAP and VAT were 9 and 12 days, respectively. Multivariate analysis identified three independently associated factors for patients having VAP compared with having VAT: underlying cerebrovascular disease [adjusted OR (aOR): 0.46; 95% CI: 0.27–0.78; P = 0.04], previous surgery (aOR: 0.68; 95% CI: 0.57–0.8; P < 0.001) and acute renal failure (aOR: 1.75; 95% CI: 1.27–2.40; P = 0.001).

Conclusions

The study revealed high incidences of MDR GNB-VAT and -VAP among mechanically ventilated patients. The independent risk factors for having VAP can help identify patients at risk for developing VAP and who need early weaning from mechanical ventilation.
Public perception and community-level impact of national action plans on antimicrobial resistance in Vietnam
Authors: Thomas Shruthi Anna , Mathew Philip , Ranjalkar Jaya , Nguyen Thi Bich Van , Giao Vu Thi Quynh , Chandy Sujith J
Published: December 2023

Objectives

Vietnam was the first country from the WHO Western Pacific Region to adopt a national action plan (NAP) on antimicrobial resistance (AMR) in 2013. The multilayered nature of AMR requires coordination across ‘One Health’ sectors, dedicated financing, multistakeholder involvement, and widespread community engagement to implement the action plans. This study explores the perceived impact of NAP implementation at the community level.

Methods

Key informant interviews (KIIs) were used for data collection during 2021. An interview tool was used for the KIIs and purposive sampling was used to identify study participants from Vietnam. The study participants were those engaged with a substantial scale of antimicrobial usage, diagnosis of infections or concerned with antimicrobial content in effluents in their professional life. Twelve KIIs were conducted with participants from human health, animal health and the environmental sector. The data were entered into Microsoft Excel, and manifest and latent content analysis was done.

Results

The analysis highlighted themes such as limited public awareness of AMR, ongoing capacity building and quality assurance initiatives, implementation of guidelines and regulations for AMR containment, sustained investment in improving infrastructure, and challenges relating to accountability whilst prescribing and selling antibiotics.

Conclusions

There were many positive critical developments during the NAP implementation period in Vietnam towards AMR mitigation. For better impact, there is a need to revitalize the implementation machinery of NAPs by improving the enforcement capacity of regulations, cross-sectoral collaboration and promoting community ownership.
Adenomyoepithelioma of the Breast: Radiologic-Pathologic Correlation and Management
Authors: Smith Katherine A , Solanki Malvika H , Glazebrook Katrina N
Published: December 2023

Adenomyoepithelioma (AME) is a rare, usually benign breast neoplasm with low potential for malignant transformation. Imaging features are nonspecific and overlap with other benign and malignant breast lesions. On mammography, AME most often presents as a mass, usually oval in shape, with variable reported margins. Less commonly, AME can present mammographically as an asymmetry or can be mammographically occult. Associated calcifications are uncommon. On US, AME is usually seen as a hypoechoic oval mass, but it can also manifest as a complex cystic and solid mass. On US, the majority of AME have noncircumscribed margins (indistinct, angular, or microlobulated). Internal vascularity is usually present, and posterior enhancement can be seen. Although there is limited literature on MRI features, the most frequent finding is an irregular mass with washout kinetics; T2 hyperintensity can be observed. These nonspecific and often suspicious imaging features usually merit biopsy. On histologic analysis, AME is characterized by a biphasic proliferation of myoepithelial and epithelial cells. Pathologic diagnosis can be difficult due to the variety of histologic features of AME and heterogeneity in these tumors, especially when sampling is limited, such as in core needle biopsies. Wide local surgical excision of AME is recommended due to potential for recurrence and malignant transformation.
Psychosocial work conditions and traffic safety among minibus and long-bus drivers
Authors: Amoadu Mustapha , Ansah Edward Wilson , Sarfo Jacob Owusu
Published: December 2023

Objective: This study sought to examine the association between psychosocial work factors and road traffic crashes (RTCs), and test the differences in psychosocial work factors between minibus and long-bus drivers.

Methods: This cross-sectional survey employed a convenient sampling method to collect data from 7315 long-distance minibus and long-bus drivers who operate between the Ghanaian cities, Accra and Tema and other parts of the country. The drivers answered a job content questionnaire, psychosocial safety climate scale (PSC-12), work–family conflict scale, and demographic questions on age, education, driving hours, and RTC history.

Results: The correlational analysis showed a significant association between psychosocial work factors and RTCs for the previous 2 years. Hierarchical multiple linear regression found that supervisor support, skill discretion, decision autonomy, psychological demands, PSC, and work–family conflict significantly contributed to explaining RTC rates among the drivers. Also, significant differences were found between minibus and long-bus drivers in driving hours, occurrence of near misses, RTCs, and all psychosocial work factors explored in this study except work–family conflict.

Conclusions: Psychosocial work factors directly predict RTCs among minibus and long-bus drivers. Policymakers, driver unions, and owners and managers of bus transport businesses should prioritize integrating occupational health and safety into road transport activities. Furthermore, managers and bus owners should use bottom-up communication, provide access to support services and work-family balance initiatives, flexible work schedules, and a supportive work environment to improve road safety.
Radiological imaging protection: a study on imaging dose used while planning computed tomography for external radiotherapy in Japan
Authors: Kito Satoshi , Suda Yuhi , Tanabe Satoshi , Takizawa Takeshi , Nagahata Tomomasa , Tohyama Naoki , Okamoto Hiroyuki , Kodama Takumi , Fujita Yukio , Miyashita Hisayuki , Shinoda Kazuya , Kurooka Masahiko , Shimizu Hidetoshi , Ohno Takeshi , Sakamoto Masataka
Published: December 2023

Previous studies have primarily focused on quality of imaging in radiotherapy planning computed tomography (RTCT), with few investigations on imaging doses. To our knowledge, this is the first study aimed to investigate the imaging dose in RTCT to determine baseline data for establishing national diagnostic reference levels (DRLs) in Japanese institutions. A survey questionnaire was sent to domestic RT institutions between 10 October and 16 December 2021. The questionnaire items were volume computed tomography dose index (CTDIvol), dose–length product (DLP), and acquisition parameters, including use of auto exposure image control (AEC) or image-improving reconstruction option (IIRO) for brain stereotactic irradiation (brain STI), head and neck (HN) intensity-modulated radiotherapy (IMRT), lung stereotactic body radiotherapy (lung SBRT), breast-conserving radiotherapy (breast RT), and prostate IMRT protocols. Details on the use of motion-management techniques for lung SBRT were collected. Consequently, we collected 328 responses. The 75th percentiles of CTDIvol were 92, 33, 86, 23, and 32 mGy and those of DLP were 2805, 1301, 2416, 930, and 1158 mGy·cm for brain STI, HN IMRT, lung SBRT, breast RT, and prostate IMRT, respectively. CTDIvol and DLP values in institutions that used AEC or IIRO were lower than those without use for almost all sites. The 75th percentiles of DLP in each treatment technique for lung SBRT were 2541, 2034, 2336, and 2730 mGy·cm for free breathing, breath holding, gating technique, and real-time tumor tracking technique, respectively. Our data will help in establishing DRLs for RTCT protocols, thus reducing imaging doses in Japan.
Deep learning for complex chemical systems
Authors: Li Wei , Wang Guoqiang , Ma Jing
Published: December 2023

Deep learning forms a bridge between the local features of molecular fragments/localized orbitals and the global properties of complex systems, enabling multi-scale simulations of complex chemical systems and reaction processes.
Deciphering and integrating invariants for neural operator learning with various physical mechanisms
Authors: Zhang Rui , Meng Qi , Ma Zhi-Ming
Published: December 2023

Neural operators have been explored as surrogate models for simulating physical systems to overcome the limitations of traditional partial differential equation (PDE) solvers. However, most existing operator learning methods assume that the data originate from a single physical mechanism, limiting their applicability and performance in more realistic scenarios. To this end, we propose the physical invariant attention neural operator (PIANO) to decipher and integrate the physical invariants for operator learning from the PDE series with various physical mechanisms. PIANO employs self-supervised learning to extract physical knowledge and attention mechanisms to integrate them into dynamic convolutional layers. Compared to existing techniques, PIANO can reduce the relative error by 13.6%–82.2% on PDE forecasting tasks across varying coefficients, forces or boundary conditions. Additionally, varied downstream tasks reveal that the PI embeddings deciphered by PIANO align well with the underlying invariants in the PDE systems, verifying the physical significance of PIANO.
Arabidopsis HECT and RING-type E3 Ligases Promote MAPKKK18 Degradation to Regulate Abscisic Acid Signaling
Authors: Tajdel-Zielińska Małgorzata , Janicki Maciej , Marczak Małgorzata , Ludwików Agnieszka
Published: December 2023

Mitogen-activated protein kinase (MAPK) cascades are conserved signaling pathways that transduce extracellular signals into diverse cellular responses. Arabidopsis MAPKKK18 is a component of the MAPKKK17/18-MKK3-MPK1/2/7/14 cascades, which play critical roles in abscisic acid (ABA) signaling, drought tolerance and senescence. A very important aspect of MAP kinase signaling is both its activation and its termination, which must be tightly controlled to achieve appropriate biological responses. Recently, the ubiquitin-proteasome system (UPS) has received increasing attention as a key mechanism for maintaining the homeostasis of MAPK cascade components and other ABA signaling effectors. Previous studies have shown that the stability of MAPKKK18 is regulated by the UPS via the ABA core pathway. Here, using multiple proteomic approaches, we found that MAPKKK17/18 turnover is tightly controlled by three E3 ligases, UPL1, UPL4 and KEG. We also identified lysines 154 and 237 as critical for MAPKKK18 stability. Taken together, this study sheds new light on the mechanism that controls MAPKKK17/18 activity and function.
Serum amyloid A aggravates endotoxin‐induced ocular inflammation through the regulation of retinal microglial activation
Authors: Feng Huazhang , Zhou Wenchuan , Yang Yuan , Zhang Xuerui , Mao Ruixue , Zhou Yutong , Cheng Tongjie , Xiao Haodong , Rao Yuqing , He Jincan , Zhao Peiquan , Li Jing , Jiang Chunhui
Published: December 2023

Serum amyloid A (SAA) are major acute‐phase response proteins which actively participate in many inflammatory diseases. This study was designed to explore the function of SAA in acute ocular inflammation and the underlying mechanism. We found that SAA3 was upregulated in endotoxin‐induced uveitis (EIU) mouse model, and it was primarily expressed in microglia. Recombinant SAA protein augmented intraocular inflammation in EIU, while the inhibition of Saa3 by siRNA effectively alleviated the inflammatory responses and rescued the retina from EIU‐induced structural and functional damage. Further study showed that the recombinant SAA protein activated microglia, causing characteristic morphological changes and driving them further to pro‐inflammatory status. The downregulation of Saa3 halted the amoeboid change of microglia, reduced the secretion of pro‐inflammatory factors, and increased the expression of tissue‐reparative genes. SAA3 also regulated the autophagic activity of microglial cells. Finally, we showed that the above effect of SAA on microglial cells was at least partially mediated through the expression and signaling of Toll‐like receptor 4 (TLR4). Collectively, our study suggested that microglial cell‐expressed SAA could be a potential target in treating acute ocular inflammation.
β-Arrestin-1 reduces acute myocardial infarction via promoting autophagy in cardiomyocytes
Authors: Liu Mengzhen , Yan Hui , Zhu Dan-Ni , Kong Ni , Cao Qi , Zhang Xiaoying , Wei Wei , Ke Ping , Chen Xiongwen , Liu Chong
Published: December 2023

Background and purpose:

β-Arrestins are key regulators of G protein–coupled receptor (GPCR) signaling. Through their function as scaffolding proteins, β-arrestins mediate a range of cellular signaling events. However, the role of β-arrestins during myocardial ischemia remains incompletely understood. In this study, we explored the regulatory effects of β-arrestin-1 on autophagy following myocardial infarction and sought to identify the underlying mechanism.

Methods:

Acute myocardial infarction was induced by permanent left anterior descending coronary artery ligation. Cardiac function was assessed using echocardiography. β-Arrestin-1, autophagy-related 5 (ATG5), and liver kinase B1 (LKB1) were overexpressed or knocked down using lentivirus-mediated transduction of the gene or short hairpin RNA (shRNA) in cultured primary cardiomyocytes. Oxygen-glucose deprivation (OGD) in cardiomyocytes was used to simulate cardiac ischemia in vitro. Autophagy and apoptosis were assessed by western blot, flow cytometry, and transmission electron microscopy. Cell survival and lactate dehydrogenase (LDH) release were evaluated using the respective kits.

Results:

β-Arrestin-1 knockout (KO) increased myocardial infarction size, an effect that was associated with decreased autophagy and deterioration of cardiac function. The overexpression of β-arrestin-1 significantly increased autophagy levels and decreased cell apoptosis in cardiomyocytes exposed to OGD, whereas the knockdown of β-arrestin-1 exerted the opposite effect. The protective effect of β-arrestin-1 overexpression was abrogated by ATG5 knockdown. β-Arrestin-1 KO attenuated the myocardial infarction–induced phosphorylation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). In cultured myocytes, the blockade of AMPK or the knockdown of LKB1 inhibited the β-arrestin-1–induced increase in the LC3-II/LC3-I ratio and beclin 1 expression levels and attenuated β-arrestin-1–mediated cardioprotective effects.

Conclusions:

Collectively, our findings suggested that β-arrestin-1 promotes cardiomyocyte survival under ischemic conditions via the regulation of LKB1/AMPK-dependent autophagy. These findings may be helpful in designing novel therapeutic strategies for myocardial ischemia.
Localized Cutaneous Argyria at the Site of a Prior Melanoma Excision Confirmed by Scanning Electron Microscopy With Energy Dispersive X-ray Analysis
Authors: McTighe Shane P. , Taylor Elizabeth A. , Allbritton Jill , Lewin-Smith Michael R.
Published: December 2023

Localized cutaneous argyria is a rare condition caused by the accumulation of silver particles in the skin, leading to blue–gray discoloration. Argyria may mimic melanoma and lead to misdiagnosis. We present a patient with a history of melanoma that developed a blue–gray nodule at a prior melanoma graft. The diagnosis was confirmed using scanning electron microscopy and energy dispersive x-ray analysis. These techniques differentiate argyria from melanoma and can be performed on formalin-fixed, paraffin-embedded, tissue sections. Health care providers should be alert that argyria may mimic recurrent melanoma in patients unaware of silver exposure.
Wellness Program Participation and its Association With Illness-Related Absenteeism and Turnover
Authors: Jenkins Kristi Rahrig
Published: December 2023

Objective

The aim of the study is to evaluate the possible association between health and wellness initiative (HWI) participation and illness related absenteeism (IRA) and turnover overtime.

Methods

The IRA (2016–2019) and turnover (2016–2020) analysis consisted of a time-series design. The IRA analysis used a comparison group with propensity score matching based on select demographics and linear mixed-effects regression modeling. Logistic regression was used to measure the relationship between 2016 participation in the HWI on 2017–2020 turnover.

Results

The percent increase when comparing 2016 and 2019 IRA is lower for participants (15.8%) than nonparticipants (50.0%, P > 0.001). The results also show that participating in the HWI in 2016 is associated with lower odds of subsequent turnover (odds ratio = 0.90).

Conclusions

Employers may consider implementing a comprehensive health and wellness program as part of their strategy to assist in lower IRA increases and turnover overtime.
Productivity Loss Among Opioid and Benzodiazepine Users in the United States
Authors: Thornton J. Douglas , Varisco Tyler , Bhatt, M.Econ. Prachet , Olateju Olajumoke , Shrestha Mina , Shen Chan
Published: December 2023

Objective

The aim of the study is to estimate the association between productivity losses and the use of prescription opioids and benzodiazepines among employed US adults with painful conditions.

Methods

Using Medical Expenditures Panel Survey (2010–2019), we used two-part (logistic regression and generalized linear model with zero-truncated negative binomial link) model to compare missed workdays due to illness or injury among employed adults with a painful condition.

Results

Of the eligible sample of 57,413 working US individuals, 14.65% were prescription opioid users, 2.95% were benzodiazepine users, and 1.59% were both opioid and benzodiazepine users. The predicted missed workdays were 5.75 (95% Confidence Limit [CL]: 5.58–5.92) days for benzodiazepine users, 13.06 (95% CL: 12.88–13.23) days among opioid users, and 15.18 (95% CL: 14.46–15.90) days for opioid and benzodiazepine concomitant users.

Conclusions

Concomitant use of prescription opioids and benzodiazepines was significantly associated with having more missed workdays among employed adults with documented painful conditions.
Antibiotic cement nails manufactured with threaded rods or cannulated intramedullary nails are better than those made with guidewires and do not debond
Authors: Bray Ryan , Zalikha Abdul K. , Ren Emily , Nasr Kerellos , Vaidya Rahul
Published: December 2023

Purpose:

The purpose of this study was to comparatively evaluate cement debonding at the time of removal of antibiotic cemented coated nails (ABNs) with cores made with a guidewire ($120), a regular intramedullary nail ($1100) or a threaded rod from a circular frame external fixator set ($60).

Methods:

A retrospective study was performed on 32 ABNs that had been implanted for long bone infections after intramedullary nailing. All ABNs were manufactured intraoperatively by the treating surgeon using 2 grams of vancomycin and single package of Tobramycin Simplex Cement (Stryker, Kalamazoo, MI). The powder, antibiotics, and polymer were mixed and then injected into an ABN cement mold (Bonesetter Holdings USA). Debonding was assessed at time of removal by the operating surgeon. Rates of cement debonding between the 3 groups were statistically compared.

Results:

Debonding occurred in 0/12 of the cement nails manufactured with an intramedullary nail, 0/7 threaded rod ABNs, and 6/13 guidewire ABNs. There was a significant difference in the rate of debonding between the 3 groups (P < 0.01). Removal of the remnant cement was accomplished with thin osteotomes, long pituitary rongeurs, or reamers. The canal was visualized using an arthroscope to ensure complete removal of the cement.

Conclusion:

ABNs fabricated with standard intramedullary nails or threaded rods did not lead to any debonding. Debonding of the cement from the inner core of an antibiotic nail often requires significant effort to remove the remnant cement. Given that threaded rods are often cheaper than guidewires, we recommend that ABNs be fabricated with either threaded rods or interlocking nails, but not guidewires, depending on the level of stability required.
Medical Errors Among Postgraduate Medical Students Joining The Iraqi and Arab Councils For Medical Specializations - Medical City Complex
Authors: Mahmood Deema Thamer , Kareem Niam Kamal , Abed Mays Mohammed , Al-mothaffar Ali M.J.
Published: December 2023

Background

All humans make mistakes. Unintentional medical mistakes affect patients and their families, but they can also have a negative behavioral, psychological and emotional impact on the involved healthcare practitioner or providers. These could include emotional distress, fear, feeling guilt and even depression.

Aim

This study aims to describe the events contributing to medical errors and the impact of these errors on behavior among postgraduate medical students joining the Iraqi and Arabic councils for medical specialty.

Subjects and Methods

A cross-sectional study was conducted in Medical city complex, Baghdad, Iraq, by convenient sampling. Data were collected by a self-administered questionnaire form, which was given to all participants and retrieved at the same day. The questionnaire contains three sections (13 items), in the first section it mainly asks about personal information of the participant and their specialty, Second section contains the main question of the study which is whether they have been involved in a medical error or not, and the third section asks about the events and behavior that are related to those errors like the time of the error, the most important contributing factor, the strongest feeling that they felt after this error and the most obvious behavioral response after the error.

Results

The total number of participants was 200 individuals. 111 of them were juniors and 89 were senior doctors. Gender (p-value< 0.0001) was significantly associated with medical errors, notably males tended to be involved in medical errors more than females with a number of 46 (40.7%) compared to 21 (24.13%) respectively. there is statistically significant association between decreased navigation of social media applications during work hours for non-work and medical error (P value < 0.0001). Furthermore, specialty was significantly associated with medical errors (P value < 0.0001) as surgical specialty tended to be involve in medical errors more than medical specialty with a number of 34 (38.2%) compared to 33(29.7%) respectively.

Conclusion

Distraction of attention was the most contributing factor behind medical errors. Emotional distress was the most common feeling experienced by participants. Increasing vigilance was the most behavioral response among participants following their involvement in medical errors. Furthermore, male doctors tend to be involved in medical errors more than female doctors. Surgical specialty tends to be involved in medical errors more than medical specialty.
A Tale of Two Parasites: A Glimpse into the RNA Methylome of Patient-derivedP. falciparumandP. vivaxisolates
Authors: Roy Priyanka , Gujarati Sukriti , Gupta Pallavi , Gupta Ishaan , Mahapatra Tanmaya , Gupta Dinesh , Kochar Sanjay Kumar , Kochar Dhanpat Kumar , Das Ashis
Published: December 2023

Understanding the molecular mechanisms of the malarial parasites in hosts is crucial for developing effective treatments. Epitranscriptomic research on pathogens has unveiled the significance of RNA methylation in gene regulation and pathogenesis. We present the first report investigating methylation patterns determined using Nanopore Direct RNA Sequencing, to single-base resolution across RNA of P. falciparum and P. vivax from Malaria patients with hepatic dysfunction. Distinct RNA methylation profiles of N6-methyladenosine and 5-methylcytosine in the parasites suggest species-specific regulatory mechanisms. These modifications are unevenly present in the annotated regions of the mRNA, potentially influencing mRNA export and translation. Methylated antisense transcripts, splicing events and modified transcripts originating from apicoplast and mitochondrial genomes have been detected. We observe a striking overlap of differential methylation of isoforms with either of the modifications in both species. The correlation of these regulatory layers will decipher the post-transcriptional environment of malaria parasites in vivo and elucidate their inherent proteome plasticity.
SIK2: A novel negative feedback regulator of FGF signaling
Authors: Kuser-Abali Gamze , Ugurlu-Bayarslan Asli , Yilmaz Yeliz , Ozcan Ferruh , Karaer Funda , Bugra Kuyas
Published: December 2023

A wide range of cells respond to FGF2 by proliferation via activation of the Ras/ERK pathway. In this study we explored the potential involvement of serine/threonine kinase SIK2 in this cascade within retinal Müller glia. We found that SIK2 phosphorylation status and activity is modulated in an FGF2-dependent manner, possibly via ERK. With SIK2 downregulation we observed enhanced ERK activation with delayed attenuation and increased cell proliferation, while SIK2 overexpression hampered FGF-dependent ERK activation. In vitro kinase and site directed mutagenesis studies indicated that SIK2 targets the pathway element Gab1 on Ser266. This phosphorylation event weakens Gab1 interactions with its partners Grb2 and Shp2. Collectively, our results suggest that during FGF dependent proliferation process ERK-mediated activation of SIK2 targets Gab1, resulting in downregulation of the Ras/ERK cascade in a feedback loop.
A computational account of joint SSRI and anti-inflammatory treatment
Authors: Reneaux Melissa , Mayberg Helen , Friston Karl , Pinotsis Dimitris A.
Published: December 2023

We present a computational model that elucidates the interplay between inflammation, serotonin levels, and brain activity. The model delineates how inflammation impacts extracellular serotonin, while cerebral activity reciprocally influences serotonin concentration. Understanding the reciprocal interplay between the immune system and brain dynamics is important, as unabated inflammation can lead to relapsing depression. The model predicts dynamics within the prefrontal cortex (PFC) and subcallosal cingulate cortex (SCC), mirroring patterns observed in depressive conditions. It also accommodates pharmaceutical interventions that encompass anti-inflammatory and antidepressant agents, concurrently evaluating their efficacy with regard to the severity of depressive symptoms.
Chemical probes to interrogate the extreme environment of mosquito larval guts
Authors: Guzmán Lindsay E. , Wijetunge Anjalee N. , Riske Brendan F. , Massani Brooke B. , Riehle Michael A. , Jewett John C.
Published: December 2023

Mosquito control methods are vital for the spread of life-threatening illnesses such as dengue fever, malaria, and yellow fever. Vector control technologies must be selective to minimize deleterious effects to our ecosystem. Successful methods that control mosquito larva populations utilize the uniquely high alkaline nature of the midgut. Here, we present novel protected triazabutadienes (pTBD) which are deprotected under basic conditions of the larval midgut, releasing an aryl diazonium ion (ADI) that results in protein modification. The probes contain a bioorthogonal terminal alkyne handle, enabling a selective Cu-click reaction with an azido-fluorophore for quantification by SDS PAGE and visualization using fluorescence microscopy. A control TBD, unable to release an ADI, did not label the midgut. We envision our chemical probes will aid in the development of new selective mosquito control methods thus preventing the spread of mosquito-borne illnesses with minimal impact on other organisms in the ecosystem.
Preclinical studies with ground germinated barley (GGB) for oral enzyme replacement therapy (Oral-ERT) in Pompe disease knockout mice
Authors: Martiniuk Frank , Mack Adra , Martiniuk Justin , Meinke Peter , Schoser Benedikt , Hu Gongshe , Kambitsis Angelo , Arvanitopoulos John , Arvanitopoulos Elena , Tchou-Wong Kam-Meng
Published: December 2023

Genetic deficiency of lysosomal acid maltase or acid α-glucosidase (GAA) results in the orphan disease known as glycogen storage disease type II or acid maltase deficiency (AMD) or Pompe disease (PD), encompassing at least four clinical subtypes of varying severity. PD results from mutations in theGAAgene and deficient GAA activity, resulting in the accumulation of glycogen in tissues (primarily muscle) and characterized by progressive skeletal muscle weakness and respiratory insufficiency. The current approved enzyme replacement therapy (ERT) for PD is via intravenous infusion of a recombinant human GAA (rhGAA) secreted by CHO cells (Myozyme, Sanofi-Genzyme) given once every 2 weeks and has shown varying efficacy in patients. Although the current ERT has proven to be very efficient in rescuing cardiac abnormalities and extending the life span of infants, the response in skeletal muscle is variable. In late-onset patients, only mild improvements in motor and respiratory functions have been achieved and the current ERT is unsatisfactory in the reversal of skeletal muscle pathology. Additional challenges for ERT include insufficient targeting/uptake of enzyme into disease-relevant tissues, poor tolerability due to severe ERT-mediated anaphylactic and immunologic reactions and the prohibitively high cost of lifelong ERT ($250-500K/year adult patient). A consensus at a Nov.-2019 US Acid Maltase Deficiency Association conference suggested that a multi-pronged approach including gene therapy, diet, exercise, etc. must be evaluated for a successful treatment. Our objective is to develop an innovative and affordable approach via barley GAA (bGAA) from ground germinated barley (GGB) or liquid GGB (L-GGB) for Oral-ERT for PD or as a daily supplement to Myozyme. To this end, we hypothesize that a bGAA produced in germinated barley can be ingested daily that allows the maintenance of a therapeutic level of enzyme. We have shown in extensive preliminary data thatGGBorL-GGBwas (1) enzymatically active, (2) was taken up by GAA KO mice and human WBCs to reverse the enzyme defect that was blocked by mannose-6-phosphate, (3) hydrolyzed glycogen, (4) increased significant changes in the clinical phenotype towards the WT levels in GAA KO mice dose-dependently, (5) taken up by PD myoblasts, lymphoid/fibroblasts cells to reverse the defect, (6) bGAA was ∼70kD, (7) Km, Vmax, pH optima, inhibitors and kinetics was similar to human placental GAA and an rhGAA and (8) was strain specific.
The relationship of job characteristics with in-role and extra-role performance: the mediating effect of job crafting
Authors: Mihalca Loredana , Ratiu Lucia , Helm Christoph , Brendea Gabriela , Metz Daniel
Published: December 2023

Purpose

Drawing upon the job demands-resources model, the purpose of this study is to investigate the differential relevance of contextual antecedents for job crafting dimensions (i.e. increasing structural and social job resources) and consequently for various aspects of work performance (in-role and extra-role performance). Despite considerable research on the role of job autonomy and social support in predicting job crafting, little attention has been paid to how problem-solving, a knowledge job characteristic, relates to job crafting dimensions.

Design/methodology/approach

Survey data were collected from 282 employees belonging to different information technology companies in Romania. Structural equation modeling was used to examine the hypothesized relations.

Findings

Problem-solving was positively related to both job crafting dimensions, whereas social support was positively related only to increasing social job resources. Unexpectedly, job autonomy predicted increasing structural resources only when social support was high, as the post-hoc analysis indicated. Furthermore, increasing structural job resources fully mediated the relationship of problem-solving with in-role performance and different types of extra-role behaviors, whereas increasing social resources did not act as a mediator.

Originality/value

The current study is the first to show that problem-solving is an important predictor for job crafting. Furthermore, this study contributes to the literature by revealing that crafting structural resources represents an important mechanism that explains the positive relationship between work design (i.e. problem-solving) and different performance facets.