bluuebunny/crossref_metadata_2025 huggingface dataset:
An intrinsic polymer electrolyte via in situ cross-linked for solid lithium-based batteries with high performance
Authors: Li Chen , Hu Ajuan , Zhang Xinan , Ni Hongbin , Fan Jingmin , Yuan Ruming , Zheng Mingsen , Dong Quanfeng
Published: September 2023

Since the introduction of poly(ethylene oxide) (PEO)-based polymer electrolytes more than 50 years, few other real polymer electrolytes with commercial application have emerged. Due to the low ion conductivity at room temperature, the PEO-based electrolytes cannot meet the application requirements. Most of the polymer electrolytes reported in recent years are in fact colloidal/composite electrolytes with plasticizers and fillers, not genuine electrolytes. Herein, we designed and synthesized a cross-linked polymer with a three-dimensional (3D) mesh structure which can dissolve the Li bis(trifluoromethylsulfonyl)imide (LiTFSI) salt better than PEO due to its unique 3D structure and rich oxygen-containing chain segments, thus forming an intrinsic polymer electrolyte (IPE) with ionic conductivity of 0.49 mS cm−1 at room temperature. And it can hinder the migration of large anions (e.g. TFSI−) in the electrolyte and increase the energy barrier to their migration, achieving Li+ migration numbers (tLi+) of up to 0.85. At the same time, IPE has good compatibility with lithium metal cathode and LiFePO4 (LFP) cathode, with stable cycles of more than 2,000 and 700 h in Li//Li symmetric batteries at 0.2 and 0.5 mAh cm−2 current densities, respectively. In addition, the Li/IPE/LFP batteries show the capacity retention >90% after 300 cycles at 0.5 C current density. This polymer electrolyte will be a pragmatic way to achieve commercializing all-solid-state, lithium-based batteries.
Trajectories of Adherence to Home-Based Exercise Recommendations Among People With Low Back Pain: A Longitudinal Analysis
Authors: Arensman Remco M , Heymans Martijn W , Kloek Corelien J J , Ostelo Raymond J W G , Veenhof Cindy , Koppenaal Tjarco , Pisters Martijn F
Published: September 2023

Objective

This study aimed to examine the presence of distinct trajectories of adherence to home-based exercise recommendations among people with low back pain (LBP). This study also aimed to identify differences in baseline characteristics among groups.

Methods

This study was a secondary analysis of a prospective, multicenter cluster randomized controlled trial investigating the cost-effectiveness of a stratified blended physical therapist intervention compared to usual care physical therapy in patients with LBP. The intervention group received usual care with integrated support via a smartphone app. A total of 208 patients were recruited from 58 primary care physical therapist practices. Baseline data included patient characteristics, physical functioning, pain intensity, physical activity, fear avoidance, pain catastrophizing, self-efficacy, self-management ability, and health-related quality of life. The Exercise Adherence Scale (score range = 0–100) was used to measure adherence during each treatment session. Latent class growth analysis was used to estimate trajectories of adherence.

Results

Adherence data were available from 173 out of 208 patients (83%). Data were collected during an average of 5.1 (standard deviation [SD] = 2.5) treatment sessions, with total treatment duration of 51 (SD = 41.7) days. Three trajectory classes were identified: “declining adherence” (12%), “stable adherence” (45%), and “increasing adherence” (43%). No differences in baseline characteristic were found between groups.

Conclusion

Three adherence trajectories to exercise recommendations were identified in patients with LBP. However, baseline characteristics cannot identify a patient’s trajectory group.

Impact

Despite the presence of distinct trajectories of adherence in patients with LBP, physical therapists should not attempt to place a patient in a trajectory group at the start of treatment. Instead, adherence should be closely monitored as treatment progresses and supported when required as part of an ongoing process.
Detection and Differentiation of Xanthomonas translucens Pathovars translucens and undulosa from Wheat and Barley by Duplex Quantitative PCR
Authors: Fu Heting , Fleitas María Constanza , Sarkes Alian , Wang Lipu , Yang Yalong , Zahr Kher , Harding Michael W. , Feindel David , Kutcher Randy , Feng Jie
Published: September 2023

Two probe-based quantitative PCR (qPCR) systems, namely P-Xtt and P-Xtu, were developed to diagnose cereal bacterial leaf streak pathogens Xanthomonas translucens pv. translucens and pv. undulosa, respectively. P-Xtt is specific to pv. translucens, and P-Xtu is specific to pv. undulosa, pv. cerealis, pv. secalis, and pv. pistaciae. P-Xtt and P-Xtu worked on all accessible strains of pv. translucens and pv. undulosa, respectively. Both systems could detect 100 copies of the target gBlock DNA. The two systems could be used in both singleplex qPCR and duplex qPCR with similar efficiencies. On genomic DNA from strains of various X. translucens pathovars, both singleplex and duplex qPCR could specifically detect and differentiate pv. translucens and pv. undulosa. The duplex qPCR could detect pv. translucens and pv. undulosa from genomic DNA of 1,000 bacterial cells. On infected barley and wheat grain samples and on one infected wheat leaf sample, the duplex qPCR showed similar efficiency compared to a previously published qPCR system but with the additional capability of pathovar differentiation. The duplex qPCR system developed in this study will be useful in studies on bacterial leaf streak and detection/differentiation of the pathogens.
UBE1C is upregulated and promotes neddylation of p53 in lung cancer
Authors: Liu Hsun , Shih Yung‐Hsin , Wang Wen‐Lun , Chang Wei‐Lun , Wang Yi‐Ching
Published: September 2023

NEDDylation is a type of protein post‐translational modification that has high similarity to ubiquitination. UBE1C encodes NEDDylation E1 enzyme, locates at chromatin region 3p14.1 and shows high gene dosage amplification frequency in both Asian and Caucasian lung cancer patients. However, its NEDDylation substrates and roles in tumorigenesis remain elucidated. In this study, we aim to investigate the oncogenic role of UBE1C and its involvement in how NEDDylation regulates p53 in lung cancer. We found that UBE1C mRNA overexpression and DNA amplification in most of the lung cell lines and cancer patients. Patients with UBE1C overexpression showed poor prognosis. Moreover, we demonstrated that overexpression of UBE1C and NEDD8, a NEDDylation moiety, resulted in the p53 NEDDylation with inhibition of p53 acetylation at K373 residue. Importantly, UBE1C‐mediated NEDDylation downregulated the transcriptional activity of p53 by inhibiting p53 ability to target promoter regions of its downstream transcription targets, consequently inhibiting the promoter activities and the expression of mRNA and protein of the p53 downstream genes including p21 and PTEN. In addition, UBE1C and NEDD8 overexpression promoted migration, invasion, and proliferation of lung cancer cells. Our findings suggest that UBE1C acts as an oncogene with prognostic potential and highlight a potential role of UBE1C‐mediated NEDDylation in downregulation of p53 transcriptional activity in lung cancer.
Euglycemic diabetic ketoacidosis in a patient on sodium-glucose cotransporter 2 inhibitors
Authors: Hammond Daniel B. , Ingram Claire C.
Published: September 2023

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel drug class for treating type 2 diabetes and are unique among diabetes medications because they increase urinary glucose excretion. SGLT2 inhibitors also have shown benefit beyond reducing blood glucose in patients with cardiovascular disease, renal disease, or heart failure. The American Diabetes Association recommends SGLT2 inhibitors for patients with type 2 diabetes who have one or more of these comorbidities. This article discusses one life-threatening adverse reaction to SGLT2 inhibitors, euglycemic diabetic ketoacidosis, and recommendations about patients on SGLT2 inhibitors who need surgery.
Pacemaker-induced cardiomyopathy
Authors: Fletcher-Hall Shirley
Published: September 2023

Chronic right ventricular (RV) pacing is an often-unrecognized cause of cardiomyopathy, despite research that has revealed that chronic RV pacing can cause significant cardiomyopathy and heart failure, leading causes of hospitalization in the United States. Studies have found that chronic RV apical pacing results in ventricular dyssynchrony, reduced cardiac function, and heart failure. This article describes the deleterious effects of permanent cardiac pacemakers and their association with cardiomyopathy and heart failure. More research is needed to investigate other forms of pacing and treatment to prevent ventricular dyssynchrony and myocardial remodeling.
Upper extremity trauma in Costa Rica - Evaluating epidemiology and identifying opportunities
Authors: Castro Appiani Luis Miguel , Castro Samuel , Romero Brenda , Díaz Salas Juan Diego , Vindas Paula , Soto Rolando , Castro Artavia Cristhian , Kamal Robin N. , Shapiro Lauren M.
Published: September 2023

Background:

Traffic accidents and musculoskeletal injuries represent a major cause of morbidity and mortality in Costa Rica. To inform capacity building efforts, we conducted a survey study of hand and upper extremity (UE) fellowship-trained surgeons in Costa Rica to evaluate the epidemiology, complications, and challenges in care of UE trauma.

Methods:

Aiming to capture all hand and UE trained surgeons in Costa Rica, we compiled a list of nine surgeons and sent a survey in Spanish using Qualtrics. Assessment questions were developed to understand the burden, complications, practice patterns, challenges, and capacity associated with care of UE trauma. Questions were designed to focus on opportunities for future investigation. Questions were translated and adapted by two bilingual speakers. Data were reported descriptively and open-ended responses were analyzed using content analysis.

Results:

Nine (100%) surgeons completed the survey. Distal radius fractures, hand and finger fractures, and tendon injuries are the most frequently noted conditions. Stiffness and infection are the most common complications. About 29% of patients are unable to get necessary therapy and 13% do not return for follow-up care with monetary, distance, and transportation limitations being the greatest challenges.

Conclusions:

The burden of UE trauma in Costa Rica is high. Identifying common conditions, complications, challenges, and capacity allows for a tailored approach to partnership and capacity building (e.g. directing capacity building and/or research infrastructure toward distal radius fractures). These insights represent opportunities to inform community-driven care improvement and research initiatives, such as Delphi consensus approaches to identify priorities or the development of outcome measurement systems.
Impact of interaction between interleukin-6 gene polymorphism and Helicobacter pylori infection on susceptibility to gastric cancer
Authors: Wang Longyue , Xiao Shuaishuai , Zheng Yiming , Gao Zefeng , Fan Fan
Published: September 2023

Objective

This study aimed to evaluate the association between four single nucleotide polymorphisms (SNPs) of the interleukin-6 (IL-6) gene and gastric cancer (GC), and impact of interaction between IL-6 SNPs and Helicobacter pylori (H. pylori) infection on susceptibility to GC.

Methods

Logistic regression was used to test the relationships between four SNPs of IL-6 gene and GC susceptibility. A generalized multifactor dimensionality reduction (GMDR) model was employed to assess the interaction effect between IL-6 gene and H. pylori infection on GC risk.

Results

Logistic regression analysis indicated that the rs1800795-C allele was associated with increased GC risk, adjusted ORs (95% CI) were 1.80 (1.21–2.41) (CC vs. GG) and 1.68 (1.09–2.30) (C vs. G), respectively. The rs10499563-C allele was associated with decreased risk of GC, and adjusted ORs (95% CI) were 0.62 (0.31–0.93) (TC vs. TT), 0.52 (0.18–0.89) (CC vs. TT) and 0.60 (0.29–0.92) (C vs. T), respectively. GMDR methods found a two-dimensional model combination (including rs1800795 and H. pylori infection) was statistically significant. The selected model had testing balanced accuracy of 59.85% and the best cross-validation consistencies of 10/10 (P = 0.0107). Compared with H. pylori-negative subjects with rs1800795- GG genotype, H. pylori-positive participants with GC or CC genotype had the highest risk of GC, the OR (95% CI) was 3.34 (1.78–4.97).

Conclusion

The rs1800795-C allele was associated with increased GC risk and the rs10499563-C allele was associated with decreased GC risk. The interaction between rs1800795 and H. pylori infection was also correlated with increased risk of GC.
Primary malignant bone tumors incidence, mortality, and trends in China from 2000 to 2015
Authors: Xi Yunfeng , Qiao Liying , Na Buqi , Liu Huimin , Zhang Siwei , Zheng Rongshou , Wang Wenrui , Sun Kexin , Wei Wenqiang , He Jie
Published: September 2023

Background:

Primary malignant bone tumors are uncommon, and their epidemiological features are rarely reported. We aimed to study the incidence and death characteristics of bone tumors from 2000 to 2015.

Methods:

Population-based cancer registries submitted registry data to National Central Cancer Registry of China (NCCRC). The data collected from 501 local cancer registries in China were assessed using NCCRC screening methods and criteria. Incidence and mortality rates of primary bone tumor were stratified by age group, gender, and area. Age-standardized incidence and mortality rates were adjusted using the Chinese standard population in 2000 and Segi's world population. The annual percentage change (APC) in rate was calculated using the Joinpoint Regression Program.

Results:

Data from 368 registries met quality control criteria, of which 134 and 234 were from urban and rural areas, respectively. The data covered 309,553,499 persons. The crude incidence, age-standardized incidence, and crude mortality rates were 1.77, 1.35, and 1.31 per 100,000, respectively. Incidence and mortality rates were higher in males than those in females; they showed downward trends, with declines of 2.2% and 4.8% per year, respectively, and the rates in urban areas were lower than those in rural areas. Significant declining trends were observed in urban areas. Stable trends were seen in rural areas during 2000 to 2007, followed by downward trends. Age-specific incidence and mortality rates showed stable trends in the age group of 0 to 19 years, and downward trends in the age group elder than 19 years.

Conclusions:

The incidence and mortality rates of primary malignant bone tumors in rural areas were higher compared to those in urban areas. Targeted prevention measures are required to monitor and control bone tumor incidence and improve the quality of life of affected patients. This research can provide a scientific basis for the prevention and control of bone tumors, as well as basic information for follow-up research.
Ethanol Embolotherapy for Cutaneous Erythema of High-Flow Vascular Malformations in the Head and Neck
Authors: Zhou Jingwei , Hua Chen , Yang Xi , Jia Hechen , Yu Wenxin , Jin Yunbo , Lin Xiaoxi
Published: September 2023

BACKGROUND

Cutaneous erythema is one of the most common signs of arteriovenous malformations (AVMs) in the head and neck region, influencing aesthetic appearance. Surgical resection of AVMs may lead to cicatrization of the skin or aggravation of the lesion. Laser treatment, although effective in improving superficial vascular lesions, cannot prevent deep AVMs from further development.

OBJECTIVE

The authors propose an absolute ethanol embolization therapy that can effectively and safely eradicate the nidus with a favorable aesthetic outcome.

METHODS

The authors conducted a retrospective observational study of 14 AVM patients with distinct cutaneous erythema in the head and neck region undergoing embolotherapy in a single primary care center. Symptoms before and after treatment, complications, and degree of devascularization were recorded and assessed. Changes in cutaneous redness were evaluated using a previously reported quantitative measurement.

RESULTS

Complete symptomatic relief was observed in 5 patients, and major improvement was observed in 9 patients. The mean Δa* value of the color change had a significant reduction of 6.50 ± 4.04, p < .001, indicating a remarkable remission of cutaneous erythema.

CONCLUSION

Ethanol embolization is an effective and safe treatment for head and neck AVMs with excellent aesthetic outcomes and might become a potential treatment method for other superficial vascular anomalies.
Vascular regenerative cells in cardiometabolic disease
Authors: Bakbak Ehab , Krishnaraj Aishwarya , Park Brady , Verma Subodh , Hess David A.
Published: September 2023

Purpose of review

This review will provide an overview of the recent literature linking the pathophysiology of cardiometabolic disease with the depletion and dysfunction of circulating vascular regenerative (VR) cell content. Moreover, we provide rationale for the use of VR cells as a biomarker for cardiovascular risk and the use of pharmacological agents to improve VR cell content.

Recent findings

Recent studies demonstrate the potential of VR cells as a biomarker of cardiovascular risk and as a therapeutic target. Notably, lipid-lowering agents, antihyperglycemic therapies such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, as well as exercise and weight loss, have all been found to improve VR cell content, providing mechanistic evidence supporting a role in mitigating adverse cardiovascular outcomes in people with cardiometabolic-based disease.

The importance of VR cells as a biomarker in assessing cardiovascular risk is becoming increasingly apparent. This review highlights recent literature supporting the accurate use of VR cell characterization to monitor the capacity for vessel repair and novel strategies to improve vessel health. Future research is required to validate and optimize these emerging approaches.
LATE RECURRENCE OF RETINAL DETACHMENT: INCIDENCE, CLINICAL FEATURES AND SURGICAL OUTCOMES
Authors: Anguita Rodrigo , Makuloluwa Achini , Sim Sing Yue , Flores-Sanchez Blanca , Roth Janice , Charteris David G
Published: September 2023

Purpose:

To describe and evaluate demographics, clinical features, prognostic factors, rate of success of surgery, incidence and visual outcomes in patients with a late recurrence of rhegmatogenous retinal detachment(RRD) over a 10-year period at a large tertiary referral eye centre.

Methods:

A retrospective, observational case-series of patients with late recurrence of retinal detachment, defined as redetachment after at least 6 months of total reattachment in non-PVR RRD, after vitrectomy(PPV) surgery with gas tamponade.

Results:

39 patients with a late recurrence of RRD out of 16,396 RRD operations. The mean of time between the first RD surgery and redetachment was 122.7 weeks(SD 115). On presentation with late recurrence, 72% of eyes were pseudophakic and 64% were macula-off. In 28 eyes small breaks were found. 38% had established PVR,(PVR-C in 80 %). 95% underwent PPV. Gas was used in 61%.The initial secondary success rate was 41%. Initial BCVA was 1.32 logMAR(6/120) and final was 0.8 logMAR(6/38)(p-value 0.002).

Conclusion:

Late recurrence of retinal detachment is rare. It is characterized by small retinal breaks which may be difficult to visualise. Although cases can be treated with favourable anatomical results, visual outcomes are often less good, the success rate is lower.
Reproductive Factors and the Risk of Open Angle Glaucoma in Women
Authors: Kai Jia-Yan , Zhou Miao , Li Dan-Lin , Zhu Ke-Yao , Zhang Xiao-Feng , Pan Chen-Wei
Published: September 2023

Précis:

There was a significant inverse linear relationship between age at menopause and open angle glaucoma (OAG). Late menarche (≥13 y) and a history of 5 or more deliveries were significantly associated with an increased risk of OAG.

Purpose:

To determine the association between reproductive factors including age at menarche, age at menopause, reproductive period, parity, and the risk of OAG in women.

Methods:

PubMed, Embase, Cochrane Library, and Web of Science were searched until February 9, 2022. Studies were included if they assessed the association between reproductive factors and OAG. The adjusted odds ratios (ORs) with relevant 95% CIs were extracted and pooled using fixed-effects models. Besides, we conducted dose-response analyses via the generalized least squares for trend method.

Results:

Seven articles including 18,618 women were identified in this review. The pooled results indicated that late age at menarche (≥13 y) was significantly associated with an increased risk of OAG (OR=1.76, 95% CI: 1.28, 2.43). Early menopause (<45 y) also significantly elevated the risk of OAG (OR=1.89, 95% CI: 1.23, 2.90) in categorical meta-analyses, consistent with the inverse linear relationship between menopausal age and the risk of OAG in dose-response analyses (P=0.002). In addition, women who had delivered at least 5 children were at significantly higher risk of OAG compared with those nulliparous (OR=2.35, 95% CI: 1.02, 5.39), and a J-shape relationship between parity and OAG was observed in dose-response analyses (P<0.001).

Conclusions:

Late menarche (≥13 y), early menopause (<45 y), and a history of 5 or more parturitions are possible risk factors for OAG. Longitudinal studies are warranted to further examine the relationships between reproductive factors and the risk of OAG.
Trabeculectomy in Eyes With High Myopia
Authors: Abe Ricardo Y. , Oltramari Laura , Vessani Roberto M. , Schimiti Rui B. , Magacho Leopoldo , Kanadani Fábio N. , Costa Vital P.
Published: September 2023

Précis:

Primary trabeculectomy was safe and effective at lowering intraocular pressure (IOP) in patients with primary open angle glaucoma and high myopia.

Purpose:

To investigate the efficacy and safety of trabeculectomy in patients with glaucoma and high myopia.

Patient and Methods:

Retrospective case-control study. Glaucomatous patients with high myopia undergoing primary trabeculectomy surgery with at least 1 year of follow-up were compared with an age-matched control group without high myopia undergoing the same procedure. Surgical success was defined as: IOP ≤ 15 mm Hg with (qualified) or without (complete) antiglaucoma medications and at least 20% reduction from baseline IOP at the end of 48 months of follow-up.

Results:

We included a total of 90 eyes from 90 patients (45 eyes with high myopia and 45 controls). Within the 90 eyes, 70 eyes underwent trabeculectomy and 20 eyes underwent combined phacoemulsification and trabeculectomy. Although patients with high myopia had higher chances for failure (37% vs. 22%) compared with controls, the difference was not statistically significant (P=0.067). In the multivariable analysis, patients of African descent (P=0.043) and those with juvenile glaucoma (P=0.001) had more chances of failure, even after adjusting for myopia. There was no statistically significant difference between complication rates in both groups.

Conclusion:

Trabeculectomy was effective in reducing IOP in patients with high myopia and glaucoma, without the additional risk of complications compared with a control group.
An Evaluation Framework for a Novel Process to Codevelop Written and Computable Guidelines
Authors: Tailor Amrita , Robinson Susan J. , Matson-Koffman Dyann M. , Michaels Maria , Burton Matthew M. , Lubin Ira M. ,   on behalf of the Workgroup on Evaluation of the Integrated Process
Published: September 2023

Clinical practice guidelines (CPGs) support individual and population health by translating new, evidence-based knowledge into recommendations for health practice. CPGs can be provided as computable, machine-readable guidelines that support the translation of recommendations into shareable, interoperable clinical decision support and other digital tools (eg, quality measures, case reports, care plans). Interdisciplinary collaboration among guideline developers and health information technology experts can facilitate the translation of written guidelines into computable ones. The benefits of interdisciplinary work include a focus on the needs of end-users who apply guidelines in practice through clinic decision support systems as part of the Centers for Disease Control and Prevention’s (CDC’s) Adapting Clinical Guidelines for the Digital Age (ACG) initiative, a group of interdisciplinary experts proposed a process to facilitate the codevelopment of written and computable CPGs, referred to as the “integrated process (IP).”1 This paper presents a framework for evaluating the IP based on a combination of vetted evaluation models and expert opinions. This framework combines 3 types of evaluations: process, product, and outcomes. These evaluations assess the value of interdisciplinary expert collaboration in carrying out the IP, the quality, usefulness, timeliness, and acceptance of the guideline, and the guideline’s health impact, respectively. A case study is presented that illustrates application of the framework.
Impact of Prolonged Ischemia on the Immunohistochemical Expression of Programmed Death Ligand 1 (PD-L1)
Authors: Barberà Angels , González Juan , Martin Montserrat , Mate Jose L. , Oriol Albert , Martínez-Soler Fina , Santalucia Tomas , Fernández Pedro Luis
Published: September 2023

Antibodies targeting programmed death receptor 1 or programmed death ligand 1 (PD-L1) have become a standard of care to treat different cancers; for some of these tumors, there is a correlation between tissue expression of PD-L1 and response rates in patients. Although most of the analytical challenges in the evaluation of PD-L1 expression have been standardized, preanalytical issues have been less explored. The objective of this study was to evaluate the impact of time of ischemia on the performance of 2 commonly used antibodies against PD-L1. Sixteen tonsillectomy samples were kept in ischemia for <30 minutes from sample obtention (control) and 1, 3, 6, 12, and 24 hours at room temperature before formalin fixation and paraffin embedding. Selected areas were inserted into TMA paraffin recipient blocks stained with SP142 and SP263 antibodies and evaluated by 2 blind observers. The proportion of suboptimally stained samples was significantly higher for samples with cold ischemia times 6 hours or over (P<0.0001). False-negative results were 25% in samples exposed to 6 hours of ischemia and raised to 34% for samples remaining in ischemia for 12 or 24 hours. When all observations were pooled, SP142 provided suboptimal results in 24% of observations and SP263 in 12.5%; this is a statistically significant difference (P=0.042). In conclusion, the quality of staining for PD-L1 in tonsil samples varies with the time of cold ischemia. The SP142 antibody presented a significantly lower tolerance to prolonged cold ischemia than SP263. These results reveal the relevance of controlled preanalytical processing of samples.
Expression of TLE1 in a Carcinoid Tumor of the Lung With Spindle Cell Morphology—A Potential Diagnostic Pitfall
Authors: Jeffus Susanne K. , Meena Nikhil , Lindberg Matthew
Published: September 2023

Tumors of the lung with a spindle cell morphology require consideration of many entities in the differential diagnosis, including metastases. Ancillary immunohistochemical stains but also molecular studies are typically required to arrive at the proper diagnosis. We present a case of a 71-year-old woman with multiple lung nodules, mediastinal lymphadenopathy, and a history of uterine cancer who underwent endobronchial ultrasound-guided fine needle aspiration and biopsy of the lung and mediastinal lymph nodes. A sampling of the lung lesion showed a cytologically bland neoplasm with spindle cell morphology, lacking necrosis or brisk mitotic activity. In conjunction with the cytomorphology, strong and diffuse Transducin-like enhancer of split 1 (TLE1) reactivity in the tumor cells initially raised the diagnosis of synovial sarcoma; however, subsequent results of additional testing showed strong and diffuse expression with AE1/AE3, CK 8/18, TTF-1, synaptophysin and chromogranin and focal or negative staining with a large number of other antibodies. This warranted a diagnosis of a carcinoid tumor. This is the first report of TLE1 staining in a carcinoid tumor of the lung. Therefore, when evaluating tumors of the lung with spindle cell morphology in which the differential diagnosis may include both carcinoid tumor and synovial sarcoma, TLE1 expression should be interpreted with caution and in conjunction with an expanded immunohistochemical staining panel.
Uterine Sarcoma With EML4::NTRK3 Fusion: A Spectrum of Mesenchymal Neoplasms Harboring Actionable Gene Fusions
Authors: de Castro João Víctor Alves , dos Santos Pedro José Silva , Mantoan Henrique , Baiocchi Glauco , Bovolim Graziele , Torrezan Giovana , Corassa Marcelo , do Nascimento Antônio Geraldo , De Brot Marina , Costa Felipe D’Almeida , De Brot Louise
Published: September 2023

NTRK gene fusions are part of a paradigm shift in oncology, arising as one of the main genomic alterations with actionability in the so-called “agnostic setting.” In gynecologic pathology, the recent description of uterine sarcoma resembling fibrosarcoma and with NTRK rearrangements (NTRK-rearranged uterine sarcoma) highlights the importance of recognizing clinicopathological cues that can lead to genomic profiling. Herein, we report the case of a 43-year-old woman presenting with vaginal bleeding and pelvic mass. Histopathology of the tumor showed moderately atypical spindle cells arranged in long fascicles reminiscent of fibrosarcoma, along with immunohistochemical positivity for S100, CD34, and pan-tropomyosin receptor kinase. This prompted RNA-sequencing and the finding of a rare EML4::NTRK3 fusion. Clinical, histologic, and molecular findings are described, in addition to discussions regarding differential diagnoses and possible implications of the findings in clinical practice.
KNEE OSTEONECROSIS AFTER SARS-COV 2 VIRUS INFECTION
Authors: Muñoz García Ana , Jiménez Martín Florencio , Hernández Herrero David
Published: September 2023

Osteonecrosis after COVID-19 infection is a complex pathology with multifactorial origin. Factors such as infection itself with associated coagulopathy, as well as genetic mechanisms, and medications used for its treatment such as corticosteroids, may also be involved. The variability in the presentation makes diagnosis difficult, which, if done soon, can help delay progression and reduce morbidity and the need for surgery.

This report presents a case of knee osteonecrosis in a female patient who did not have previous knee pathology on imaging tests. She was diagnosed by magnetic resonance imaging months after hospital admission for SARS-COV 2 pneumonia, which required high-dose corticosteroid treatment.
Thermal threshold testing: call for a balance between the number of measurements and abnormalities in the diagnosis of sarcoidosis-associated small fiber neuropathy
Authors: Raasing Lisette R.M. , Veltkamp Marcel , Datema Mirjam , Grutters Jan C. , Vogels Oscar J.M.
Published: September 2023

Introduction:

Several recent studies of diagnosing small fiber neuropathy (SFN) have shown a lack of uniformity in thermal threshold testing (TTT) or quantitative sensory testing (QST) which makes it a challenge to compare the data. It is known that the chance of finding an abnormality increases with increasing number of measurements.

Objectives:

With this study, we first wanted to investigate whether TTT could benefit from a new approach focusing on the balance between the number of measurements, depending on the selection of parameters and measuring sites, and on number of abnormalities (NOAs). Second, we wanted to address the role of the method of levels (MLe) in possible desensitization during TTT measurements.

Methods:

One hundred seventeen participants were included (48 patients with sarcoidosis with probable SFN, 49 without SFN, and 20 healthy controls). Thermal threshold testing measurements and Small Fiber Neuropathy Screening List (SFNSL) questionnaire were used to assess SFN.

Results:

A combination of measuring all thermal threshold parameters at both feet except for MLe showed the best diagnostic performance. Increasing TTT NOAs correlates with the severity of SFN. Adding the SFNSL questionnaire further improves diagnostic performance.

Discussion:

Looking at TTT NOAs in all TTT parameters except for MLe at both feet should be considered as a new approach to improve the consistency and balance between the selection of TTT parameters, measuring sites, and definition of “abnormal QST.” Moreover, the SFNSL questionnaire is a valuable tool to quantify SFN symptoms and could improve SFN diagnosis.
Considering the Interaction between Surgical Approach and Timing on Complication Rates of Complex Orbital Fracture Repair
Authors: Flyer Benjamin E. , Feehs Kenneth R. , Maniscalco Brianna R. , Lacy Alexa L. , Slijepcevic Allison A.
Published: September 2023

Objective:

The optimal approach and timing of complex orbital fracture repair is an unresolved issue that is complicated by unique clinical presentations and patient-specific considerations. Early surgical repair in less than 14 days is associated with fewer complications; however, there are no guidelines addressing the optimal timing for surgical repair. This study assesses the time of surgical repair and surgical outcomes of complex orbital fractures.

Methods:

Retrospective chart review from 2010 to 2022. Adult patients with orbital fractures are treated with surgical repair.

Results:

In all, 94 patients presented with orbital fractures and were treated with 108 surgeries. Postoperative complications: vision disturbance 33/108 (30.6%), gaze restriction 12/108 (11.1%), lid malposition 10/108 (9.3%), globe complication 13/108 (12.0%), and hardware issues 14/108 (13.0%). Postoperative complications were not significantly associated with the surgical approach used for fracture repair or the time of surgical repair.

Conclusion:

Postoperative complications following surgical repair of orbital fractures are not associated with surgical approach or time of repair following the initial injury.
The effects of aging on rod bipolar cell ribbon synapses
Authors: Shrestha Abhishek P , Rameshkumar Nirujan , Boff Johane Martins , Rajmanna Rhea , Chandrasegaran Thadshayini , Courtney Frederick E , Zenisek David , Vaithianathan Thirumalini
Published: September 2023

The global health concern posed by age-related visual impairment highlights the need for further research focused on the visual changes that occur during the process of aging. To date, multiple sensory alterations related to aging have been identified, including morphological and functional changes in inner hair cochlear cells, photoreceptors, and retinal ganglion cells. While some age-related morphological changes are known to occur in rod bipolar cells in the retina, their effect on these cells and on their connection to other cells via ribbon synapses remain elusive. To investigate the effects of aging on rod bipolar cells and their ribbon synapses, we compared synaptic calcium currents, calcium dynamics, and exocytosis in zebrafish (Danio rerio) that were middle-aged (MA,18 months) or old-aged (OA, 36 months). The bipolar cell terminal in OA zebrafish exhibited a decreased number of synaptic ribbons, an increased ribbon length, and a decrease in local Ca2+signals at the tested ribbon location with little change in the overall magnitude of the calcium current or exocytosis in response to brief pulses. Staining of the synaptic ribbons with antibodies specific for PKCα revealed shortening of the inner nuclear and plexiform layers (INL and IPL). These findings shed light on age-related changes in the retina that are related to synaptic ribbons and calcium signals.
Impact of Molecular Dynamics of Polyrotaxanes on Chondrocytes in Double Network Supramolecular Hydrogels under Physiological Thermomechanical Stimulation
Authors: Stampoultzis Theofanis , Rana Vijay Kumar , Guo Yanheng , Pioletti Dominique P.
Published: September 2023

Hyaline cartilage, a soft tissue enriched with a dynamic extracellular matrix, manifests as a supramolecular system within load-bearing joints. At the same time, the challenge of cartilage repair through tissue engineering lies in replicating intricate cellular-matrix interactions. This study attempts to investigate chondrocyte responses within double-network supramolecular hydrogels, tailored to mimic the dynamic molecular nature of hyaline cartilage. To this end, we infused non-covalent host-guest polyrotaxanes, by blending α-cyclodextrins as host molecules and polyethylene glycol as guests, into a gelatin-based covalent matrix, thereby enhancing its dynamic characteristics. Subsequently, chondrocytes were seeded into these hydrogels to systematically probe the effects of varied concentrations of introduced polyrotaxanes (instilling different levels of supramolecular dynamism in the hydrogel systems) on cellular responsiveness. Our findings unveiled an augmented level of cellular mechanosensitivity for supramolecular hydrogels compared to pure covalent-based systems. This is demonstrated by an increased mRNA expression of ion channels (TREK1, TRPV4, PIEZO1), signaling molecules (SOX9) and matrix remodeling enzymes (LOXL2). Such outcomes were further elevated upon external application of biomimetic thermomechanical loading that brought a stark increase in the accumulation of sulfated glycosaminoglycans and collagen. Overall, we found that matrix adaptability plays a pivotal role in modulating chondrocyte responses within double-network supramolecular hydrogels. These findings hold potential for advancing cartilage engineering within load-bearing joints.

Graphical Abstract

Double network supramolecular hydrogels enhanced chondro-induction significantly compared to purely covalent-based hydrogels as indicated by enhanced accumulation of extracellular matrix molecules.
iLEC-DNA: Identifying Long Extra-chromosomal Circular DNA by Fusing Sequence-derived Features of Physicochemical Properties and Nucleotide Distribution Patterns
Authors: Abbasi Ahtisham Fazeel , Asim Muhammad Nabeel , Dengel Andreas , Ahmed Sheraz
Published: September 2023

Long extrachromosomal circular DNA (leccDNA) regulates several biological processes such as genomic instability, gene amplification, and oncogenesis. The identification of leccDNA holds significant importance to investigate its potential associations with cancer, autoimmune, cardiovascular, and neurological diseases. In addition, understanding these associations can provide valuable insights about disease mechanisms and potential therapeutic approaches. Conventionally, wet lab-based methods are utilized to identify leccDNA, which are hindered by the need for prior knowledge, and resource-intensive processes, potentially limiting their broader applicability. To empower the process of leccDNA identification across multiple species, the paper in hand presents the very first computational predictor. The proposed iLEC-DNA predictor makes use of SVM classifier along with sequence-derived nucleotide distribution patterns and physicochemical properties-based features. In addition, the study introduces a set of 12 benchmark leccDNA datasets related to three species, namely HM, AT, and YS. It performs large-scale experimentation across 12 benchmark datasets under different experimental settings using the proposed predictor and more than 140 baseline predictors. The proposed predictor outperforms baseline predictors across diverse leccDNA datasets by producing average performance values of 80.699%, 61.45% and 80.7% in terms of ACC, MCC and AUC-ROC across all the datasets. The source code of the proposed and baseline predictors is available athttps://github.com/FAhtisham/Extrachrosmosomal-DNA-Prediction.
Onsager’s variational principle in proliferating biological tissues, in presence of activity and anisotropy
Authors: Ackermann Joseph , Ben Amar Martine
Published: September 2023

A hallmark of biological cells is their ability to proliferate and of tissues their ability to grow. This is common in morphogenesis and embryogenesis but also in pathological conditions such as tumour growth. To consider these tissues from a physical point of view, it is necessary to derive fundamental relationships, in particular for velocities and density components, taking into account growth terms, chemical factors and the symmetry of cells and tissues. The aim is then to develop a consistent coarse-grained approach to these complex systems, which exhibit proliferation, disorder, anisotropy and activity at small scales. To this end, Onsager’s variational principle allows the systematic derivation of flux-force relations in systems out of equilibrium and the principle of the extremum of dissipation, first formulated by Rayleigh and revisited by Onsager, finally leads to a consistent formulation for a continuous approach in terms of a coupled set of partial differential equations. Considering the growth and death rates as fluxes, as well as the chemical reactions driving the cellular activities, we derive the momentum equations based on a leading order physical expansion. Furthermore, we illustrate the different interactions for systems with nematic or polar order at small scales, and numerically solve the resulting system of partial differential equations in relevant biophysical growth examples. To conclude, we show that Onsager’s variational principle is useful for systematically exploring the different scenarios in proliferating systems, and how morphogenesis depends on these interactions.
Functional and phylogenetic β diversities and their link with clustering/overdispersion and uniqueness/redundancy
Authors: Pavoine Sandrine , Ricotta Carlo
Published: September 2023

In the recent decades, research on biodiversity in community ecology has been marked by the consideration of species’ evolutionary histories and biological traits, including those said functional as they relate to the functions a species has in ecosystems. Among the different spatial levels at which FP diversity can be quantified, less attention has been given to the definition of the general concept of between-communities (β) FP diversity than to those of local, within-communities (α) and regional, merged-communities (γ) FP diversities. Here we develop a new way for partitioning FP β diversity into elementary components to underline how and why FP β diversity differs from species β diversity, the latter reflecting only differences in species’ abundances between communities. As a reference example, we consider two distinct measures of FP β diversity: Rao’s dissimilarity coefficient (Qβ) that expresses an average dissimilarity between communities, and its transformation into an equivalent number of communities (Dβ).

Thanks to analytical partitioning and simulations, we show thatQβandDβare connected differently with typical patterns of community structure. The search for the ecological and evolutionary processes that drive community assembly and the assessment of community resilience and stability have indeed revealed typical community structures: the local clustering of species with similar traits or shared evolutionary histories; and the local (α) or regional (γ) presence of functionally or phylogenetically redundant versus unique species. WhileQβandDβare both increasing functions of species β diversity and γ FP uniqueness,Qβincreases with FP clustering whileDβincreases with α FP redundancy. The selection of an index of β diversity for a given study depends on its objective, such as communication to conservation policy makers or theoretical study of the ecological and evolutionary processes of community assembly. To facilitate and secure this selection, we call, through our study, for the development of formal and precise definition(s) for FP β diversity in light of the concepts of clustering versus overdispersion, and redundancy versus uniqueness. In particular, we call for further research on when and why FP β diversity should increase with FP clustering.
Exercise training adaptations in liver glycogen and glycerolipids require hepatic AMP-activated protein kinase in mice
Authors: Hughey Curtis C. , Bracy Deanna P. , Rome Ferrol I. , Goelzer Mickael , Donahue E. Patrick , Viollet Benoit , Foretz Marc , Wasserman David H.
Published: September 2023

Regular exercise elicits adaptations in glucose and lipid metabolism that allow the body to meet energy demands of subsequent exercise bouts more effectively and mitigate metabolic diseases including fatty liver. Energy discharged during the acute exercise bouts that comprise exercise training may be a catalyst for liver adaptations. During acute exercise, liver glycogenolysis and gluconeogenesis are accelerated to supply glucose to working muscle. Lower liver energy state imposed by gluconeogenesis and related pathways activates AMP-activated protein kinase (AMPK), which conserves ATP partly by promoting lipid oxidation. This study tested the hypothesis that AMPK is necessary for liver glucose and lipid adaptations to training. Liver-specific AMPKα1α2 knockout (LAKO) and wild type (WT) mice completed sedentary and exercise training protocols. Liver nutrient fluxes were quantified at rest or during acute exercise following training. Liver metabolites and molecular regulators of metabolism were assessed. Training increased liver glycogen in WT mice, but not in LAKO mice. The inability to increase glycogen led to lower glycogenolysis, glucose production, and circulating glucose during acute exercise in trained LAKO mice. Deletion of AMPKα1α2 attenuated training-induced declines in liver diacylglycerides. In particular, training lowered the concentration of unsaturated and elongated fatty acids comprising diacylglycerides in WT mice, but not in LAKO mice. Training increased liver triacylglycerides and the desaturation and elongation of fatty acids in triacylglycerides of LAKO mice. These lipid responses were independent of differences in tricarboxylic acid cycle fluxes. In conclusion, AMPK is required for liver training adaptations that are critical to glucose and lipid metabolism.

NEW & NOTEWORTHY

This study shows that the energy sensor and transducer, AMP-activated protein kinase, is necessary for an exercise training-induced: i) increase in liver glycogen that is necessary for accelerated glycogenolysis during exercise, ii) decrease in liver glycerolipids independent of TCA cycle flux, and iii) decline in the desaturation and elongation of fatty acids comprising liver diacylglycerides. The mechanisms defined in these studies have implications for use of regular exercise or AMPK-activators in patients with fatty liver.