bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atypical Presentation of Tangier Disease—Expanding the Clinical Spectrum
Authors: Baskar Dipti , Vengalil Seena , Nashi Saraswati , Menon Deepak , Bevinahalli N Nandeesh , Thomas Aneesha , Bardhan Mainak , Sanka Sai Bhargava , Manjunath Nisha , Nalini Atchayaram 
Published: August 2023

Abstract
Tangier disease is an autosomal recessive multisystem metabolic disorder with neuromuscular manifestations including peripheral neuropathy such as multifocal mononeuropathy or pseudosyringomyelia patterns. We report a novel phenotype of Tangier disease with predominant anterior horn cell involvement. A 16-year-old adolescent girl born to consanguineous parents had a 1-year history of hip girdle weakness with waddling gait and progressive atrophy of the right leg. She had orange tonsils, prominent lingual tonsils, soft skin, distal joint laxity, diffuse hypotonia with asymmetric wasting of legs, proximodistal moderate weakness in lower limbs, and tendon reflexes were hypoactive. The creatine kinase level was 70 U/L. Serum showed an abnormally low level of high- and low-density lipoprotein. Whole-exome sequencing showed a novel likely pathogenic splice site homozygous mutation c.2542+1G > A in the ABCA1 gene at intron 17. Hence, a high degree of suspicion and search for peripheral clinical markers is needed in patients with unusual anterior horn cell syndromes.
Association between perimenopausal age and greater posttraumatic stress disorder and depression symptoms in trauma-exposed women
Authors: Michopoulos Vasiliki , Huibregtse Megan E. , Chahine E. Britton , Smith Alicia K. , Fonkoue Ida T. , Maples-Keller Jessica , Murphy Amy , Taylor Linzie , Powers Abigail , Stevens Jennifer S. 
Published: August 2023

AbstractObjectiveThis study aimed to determine the relationship between stages of the menopause transition (premenopausal, perimenopausal, and postmenopausal) on symptoms of posttraumatic stress disorder (PTSD) and depression in trauma-exposed women.MethodsA cross-sectional study conducted between 2005 and 2017 recruited and enrolled an urban community sample (n = 6,093) from nonpsychiatric medical clinic waiting rooms of Grady Memorial Hospital, a public safety net hospital in Atlanta, Georgia. Participants were female, 18 to 65 years old, and predominantly Black/African American.ResultsOf the 6,093 participants, 93.8% were Black/African American, 2.5% were White, and 3.8% were of all other races (Hispanic/Latino, Asian, multiracial). Participants younger than 40 years were categorized as premenopausal (n = 3,166), between 40 and 55 years of age were categorized as perimenopausal (n = 2,127), and older than 55 years were categorized as postmenopausal (n = 790). Menopause status was associated with total PTSD symptom severity (F2,5416= 9.61,P< 0.001), symptom severity within all three PTSD symptom clusters (avoidance/numbing symptoms:F2,5416= 7.10,P< 0.001; intrusive symptoms:F2,5416= 7.04,P< 0.001; hyperarousal symptoms:F2,5409= 8.31,P< 0.001), and depression symptom severity (F2,5148= 11.4,P< 0.001). Compared with both premenopausal and postmenopausal women, perimenopausal women reported significantly worse total PTSD symptoms, symptoms in the hyperarousal cluster, and depressive symptoms.ConclusionsThe current cross-sectional data show that symptoms of PTSD and depression in women are associated with reproductive age, such that perimenopausal women show higher symptom severity than premenopausal and postmenopausal women. Future longitudinal studies can reveal how changes in hormones over the course of the menopause transition impact the symptoms, neurobiology, and psychophysiology of PTSD.
The utility of P-I-R classification in predicting the on-treatment histological and clinical outcomes of patients with hepatitis B and advanced liver fibrosis
Authors: Chang Xiujuan , Lv Caihong , Wang Bingqiong , Wang Jing , Song Zheng , An Linjing , Chen Shuyan , Chen Yongping , Shang Qinghua , Yu Zujiang , Tan Lin , Li Qin , Liu Huabao , Jiang Li , Xiao Guangming , Chen Liang , Lu Wei , Hu Xiaoyu , Dong Zheng , Chen Yan , Sun Yameng , Wang Xiaodong , Li Zhiqin , Chen Da , You Hong , Jia Jidong , Yang Yongping 
Published: August 2023

Background and Aims:
The predominantly progressive, indeterminate, and predominantly regressive (P-I-R) classification extends beyond staging and provides information on dynamic changes of liver fibrosis. However, the prognostic implication of P-I-R classification is not elucidated. Therefore, in the present research, we investigated the utility of P-I-R classification in predicting the on-treatment clinical outcomes.

Approach and Results:
In an extension study on a randomized controlled trial, we originally enrolled 1000 patients with chronic hepatitis B and biopsy-proven histological significant fibrosis, and treated them for more than 7 years with entecavir-based therapy. Among the 727 patients with a second biopsy at treatment week 72, we compared P-I-R classification and Ishak score changes in 646 patients with adequate liver sections for the histological evaluation. Progressive, indeterminate, and regressive cases were observed in 70%, 17%, and 13% of patients before treatments and 20%, 14%, and 64% after 72-week treatment, respectively, which could further differentiate the histological outcomes of patients with stable Ishak scores. The 7-year cumulative incidence of HCC was 1.5% for the regressive cases, 4.3% for the indeterminate cases, and 22.8% for the progressive cases (p<0.001). After adjusting for age, treatment regimen, platelet counts, cirrhosis, Ishak fibrosis score changes, and Laennec staging, the posttreatment progressive had a HR of 17.77 (vs. posttreatment regressive; 95% CI: 5.55–56.88) for the incidence of liver-related events (decompensation, HCC, and death/liver transplantation).

Conclusions:
The P-I-R classification can be a meaningful complement to the Ishak fibrosis score not only in evaluating the histological changes but also in predicting the clinical outcomes.
Modified Technique to Rehabilitate American Society of Anesthesiology-III Patient, Through Flapless Procedure With Computed Tomography–Guided Surgery
Authors: Franco Rocco , Ferrari Giulia , Vazzana Giuseppe , Cicciù Marco , Minervini Giuseppe 
Published: August 2023

Purpose:
The aim was to evaluate the safety and effectiveness of a computed tomography–guided surgery implant placement with a flapless technique and immediate functional loading in an American Society of Anesthesiology-III patient.

Methods:
This technical note involved a 64-year-old American Society of Anesthesiology-III patient. Her hopeless teeth were extracted and a restorative evaluation was provided as a prosthetic reference. The surgical procedure was based on the flapless technique that let us to use local anesthesia. The authors used an All-on-4 concept restoration for maxilla and conventional fixed prosthesis procedures for jaw rehabilitation. The authors placed 4 tilted implants in the upper maxilla and 6 right implants in the jaw. Implants were loaded with a provisional prosthesis on the same day of surgery. Five months later, provisional restoration was removed; the authors placed into the ceramic crowns 2 Procera Implant Bridge (Nobel Biocare) frameworks, developed through computer-aided design/computer-aided manufacturing technology.

Conclusions:
Computed tomography–guided surgery is a minimally invasive technique that allows, through a flapless approach, safer and more predictable procedures. In this technical note, the authors achieved accurate implant placement and precise fit of restoration with natural looking appearance; this patient-oriented-treatment led to a reduced healing time with better compliance.
Electric Scooter-related Craniofacial Injuries
Authors: Akalin Bora Edim , Alten Aytaç , Gündeş Elif 
Published: August 2023

Objectives:
Injuries associated with the use of electric scooters are a serious problem in modern society and traffic in relation to their increasing frequency of use. Although injuries involving all body parts are seen in such injuries, craniofacial ones are also very common. The aim of this study was to evaluate the craniofacial and other accompanying injuries in electric scooter-related accidents in Istanbul.

Materials and Methods:
Between January 2020 and December 2022, patients with electric scooter-related trauma among the patients admitted to the emergency unit for trauma were evaluated retrospectively. All electronic medical records, CT scans, other examinations, and treatments were retrospectively reviewed, and craniofacial fractures and other injuries seen in the patients were classified.

Results:
A total of 20.358 patients were admitted to the trauma unit between January 2020 and December 2022. Two hundred ten patients (142 male, 68 female) had electric scooter-related trauma and 58.1 % of them had craniofacial injuries. Thirty patients (14.3 %) (23 male, 7 female) had craniofacial fractures, whereas 43.8 % of them had craniofacial soft tissue injuries. The nasal fracture was the most common craniofacial fracture (14 patients, 46.7%). Orbital wall and zygomaticomaxillary complex fractures were found to be the second most common fractures.

Conclusions:
The rate of electric scooter-related injuries among all trauma patients admitted to the emergency trauma unit during the mentioned period was 1.03%. The results of this study were found to be in accordance with the data in the literature. The craniofacial region is the most frequently injured body part in patients with electric scooter-related trauma, and patients should be comprehensively evaluated for possible soft tissue injuries, craniofacial fractures, and other accompanying system injuries.
Effectiveness of social distancing measures and lockdowns for reducing transmission of COVID-19 in non-healthcare, community-based settings
Authors: Murphy Caitriona , Lim Wey Wen , Mills Cathal , Wong Jessica Y. , Chen Dongxuan , Xie Yanmy , Li Mingwei , Gould Susan , Xin Hualei , Cheung Justin K. , Bhatt Samir , Cowling Benjamin J. , Donnelly Christl A. 
Published: August 2023

Social distancing measures (SDMs) are community-level interventions that aim to reduce person-to-person contacts in the community. SDMs were a major part of the responses first to contain, then to mitigate, the spread of SARS-CoV-2 in the community. Common SDMs included limiting the size of gatherings, closing schools and/or workplaces, implementing work-from-home arrangements, or more stringent restrictions such as lockdowns. This systematic review summarized the evidence for the effectiveness of nine SDMs. Almost all of the studies included were observational in nature, which meant that there were intrinsic risks of bias that could have been avoided were conditions randomly assigned to study participants. There were no instances where only one form of SDM had been in place in a particular setting during the study period, making it challenging to estimate the separate effect of each intervention. The more stringent SDMs such as stay-at-home orders, restrictions on mass gatherings and closures were estimated to be most effective at reducing SARS-CoV-2 transmission. Most studies included in this review suggested that combinations of SDMs successfully slowed or even stopped SARS-CoV-2 transmission in the community. However, individual effects and optimal combinations of interventions, as well as the optimal timing for particular measures, require further investigation.This article is part of the theme issue 'The effectiveness of non-pharmaceutical interventions on the COVID-19 pandemic: the evidence'.
Effectiveness of international border control measures during the COVID-19 pandemic: a narrative synthesis of published systematic reviews
Authors: Grépin Karen Ann , Aston John , Burns Jacob 
Published: August 2023

The effectiveness of international border control measures during the COVID-19 pandemic is not well understood. Using a narrative synthesis approach to published systematic reviews, we synthesized the evidence from both modelling and observational studies on the effects of border control measures on domestic transmission of the virus. We find that symptomatic screening measures were not particularly effective, but that diagnostic-based screening methods were more effective at identifying infected travellers. Targeted travel restrictions levied against travellers from Wuhan were likely temporarily effective but insufficient to stop the exportation of the virus to the rest of the world. Quarantine of inbound travellers was also likely effective at reducing transmission, but only with relatively long quarantine periods, and came with important economic and social effects. There is little evidence that most travel restrictions, including border closure and those implemented to stop the introduction of new variants of concern, were particularly effective. Border control measures played an important role in former elimination locations but only when coupled with strong domestic public health measures. In future outbreaks, if border control measures are to be adopted, they should be seen as part of a broader strategy that includes other non-pharmaceutical interventions.This article is part of the theme issue 'The effectiveness of non-pharmaceutical interventions on the COVID-19 pandemic: the evidence'.
Cancer-associated fibroblasts promote drug resistance inALK-driven lung adenocarcinoma cells by upregulating lipid biosynthesis
Authors: Daum Ann-Kathrin , Schlicker Lisa , Schneider Marc A. , Muley Thomas , Klingmüller Ursula , Schulze Almut , Thomas Michael , Christopoulos Petros , Sültmann Holger 
Published: August 2023

AbstractTargeted therapy interventions using tyrosine kinase inhibitors (TKIs) provide encouraging treatment responses inALK-rearranged lung adenocarcinomas, yet resistances occur almost inevitably. Apart from tumor cell-intrinsic resistance mechanisms, accumulating evidence supports a role of cancer-associated fibroblasts (CAFs) in affecting the therapeutic vulnerability of lung cancer cells. Here, we aimed to investigate underlying molecular networks shaping the therapeutic susceptibility ofALK-driven lung adenocarcinoma cells via tumor microenvironmental cues using three-dimensional (3D) spheroid co-culture settings. We show that CAFs promote therapy resistance of lung tumor cells against ALK inhibition by reducing apoptotic cell death and increasing cell proliferation. Using single-cell RNA-sequencing analysis, we show that genes involved in lipogenesis constitute the major transcriptional difference between TKI-treated homo- and heterotypic lung tumor spheroids. CAF-conditioned medium and CAF-secreted factors HGF and NRG1 were both able to promote resistance of 3D-culturedALK-rearranged lung tumor cells via AKT signaling, which was accompanied by enhancedde novolipogenesis and supression of lipid peroxidation. Notably, simultaneous targeting of ALK and SREBP-1 was able to overcome the established CAF-driven lipid metabolic-supportive niche of TKI-resistant lung tumor spheroids. Our findings highlight a crucial role of CAFs in mediating ALK-TKI resistance via lipid metabolic reprogramming and suggest new ways to overcome resistance towards molecular directed drugs by targeting vulnerabilities downstream of oncogenic signaling.
Revisiting prostate segmentation in magnetic resonance imaging (MRI): On model transferability, degradation and PI-RADS adherence
Authors: Fernandez-Quilez Alvaro , Nordström Tobias , Eftestøl Trygve , Alvestad Andreas Bremset , Jäderling Fredrik , Kjosavik Svein Reidar , Eklund Martin 
Published: August 2023

AbstractPurposeTo investigate the effect of scanner and prostate MRI acquisition characteristics when compared to PI-RADSv2.1 technical standards in the performance of a deep learning prostate segmentation model trained with data from one center (INST1), longitudinally evaluated at the same institution and when transferred to other institutions.Materials and MethodsIn this retrospective study, a nn-UNet for prostate MRI segmentation was trained with data from 204 patients from one institution (INST1) (0.50mm2in-plane, 3.6mm thickness and 16cm field of view [FOV]). Post-deployment performance at INST1 was tested with 30 patients acquired with a different protocol and in a different period of time (0.60mm2in-plane, 4.0mm thickness and 19cm FOV). Transferability was tested on 248 patient sequences from five institutions (INST2, INST3, INST4, INST5 and INST6) acquired with different scanners and with heterogeneous degrees of PI-RADS v2.1 technical adherence. Performance was assessed using Dice Score Coefficient, Hausdorff Distance, Absolute Boundary Distance and Relative Volume Difference.ResultsThe model presented a significant degradation for the whole gland (WG) in the presence of a change of acquisition protocol at INST1 (DSC:99.46±0.12% and 91.24±3.32%,P<.001; RVD:-0.006±0.127% and 8.10±8.16%,P<.001). The model had a significantly higher performance in centers adhering to PI-RADS v2.1 when compared to those that did not (DSC: 86.24±9.67% and 74.83±15.45%,P<.001; RVD: -6.50±18.46% and 1.64±29.12%,P=.003).ConclusionsAdherence to PI-RADSv2.1 technical standards benefits inter-institutional transferability of a deep learning prostate segmentation model. Post-deployment evaluations are critical to ensure model performance is maintained over time in the presence of protocol acquisition modifications.
Olfactomedin-4+neutrophils exacerbate intestinal epithelial damage and worsen host survival afterClostridioides difficileinfection
Authors: Huber A. , Jose S. , Kassam A. , Weghorn K. N. , Powers-Fletcher Maggie , Sharma D. , Mukherjee A. , Mathew A. , Kulkarni N. , Chandramouli S. , Alder M. N. , Madan R. 
Published: August 2023

AbstractNeutrophils are key first responders toClostridioides difficileinfection (CDI). Excessive tissue and blood neutrophils are associated with worse histopathology and adverse outcomes, however their functional role during CDI remains poorly defined. Utilizing intestinal epithelial cell (IEC)-neutrophil co-cultures and a pre-clinical animal model of CDI, we show that neutrophils exacerbateC. difficile-induced IEC injury. We utilized cutting-edge single-cell transcriptomics to illuminate neutrophil subtypes and biological pathways that could exacerbate CDI-associated IEC damage. As such, we have established the first transcriptomics atlas of bone marrow (BM), blood, and colonic neutrophils after CDI. We found that CDI altered the developmental trajectory of BM and blood neutrophils towards populations that exhibit gene signatures associated with pro-inflammatory responses and neutrophil-mediated tissue damage. Similarly, the transcriptomic signature of colonic neutrophils was consistent with hyper-inflammatory and highly differentiated cells that had amplified expression of cytokine-mediated signaling and degranulation priming genes. One of the top 10 variable features in colonic neutrophils was the gene for neutrophil glycoprotein, Olfactomedin 4 (OLFM4). CDI enhanced OLFM4 mRNA and protein expression in neutrophils, and OLFM4+cells aggregated to areas of severe IEC damage. Compared to uninfected controls, both humans and mice with CDI had higher concentrations of circulating OLFM4; and in mice, OLFM4 deficiency resulted in faster recovery and better survival after infection. Collectively, these studies provide novel insights into neutrophil-mediated pathology after CDI and highlight the pathogenic role of OLFM4+neutrophils in regulating CDI-induced IEC damage.One Sentence SummaryUtilizing single-cell transcriptomics, IEC-epithelial co-cultures, and pre-clinical models of CDI, we have identified a subset of neutrophils that are marked by OLFM4 expression as pathogenic determinants of IEC barrier damage after CDI.
Structural insights into DNA Topoisomerase II of African Swine Fever Virus
Authors: Cong Jingyuan , Xin Yuhui , Kang Huiling , Yang Yunge , Wang Chenlong , Li Xuemei , Rao Zihe , Chen Yutao 
Published: August 2023

AbstractType II topoisomerases are ubiquitous enzymes that play a pivotal role in modulating the topological configuration of dsDNA. These Topo Ⅱ enzymes are indispensable for DNA metabolism and have been extensively investigated in both prokaryotic and eukaryotic organisms. However, understanding of virus-encoded Topo II remains limited. One intriguing example is the African swine fever virus (ASFV), which stands as the sole mammalian-infecting virus encoding a Topo II. In this work, we utilized multiple approaches involving cryo-EM, X-ray crystallography, atomic force microscopy and biochemical assays to investigate the structure and function of ASFV Topo Ⅱ, pP1192R. We determined the structures of pP1192R in different conformational states and confirming its enzymatic activity in vitro. Collectively, our results unveil the basic mechanisms of viral Topo II, thereby not only augmenting our understanding of this kind of intriguing enzymes but also presenting a potential avenue for the intervention strategies to mitigate the impact of African swine fever virus.
A non-genetic model of vascular shunts informs on the cellular mechanisms of formation and resolution of arteriovenous malformations
Authors: Ouarné Marie , Pena Andreia , Ramalho Daniela , Conchinha Nadine V. , Costa Tiago , Figueiredo Ana , Saraiva Marta Pimentel , Carvalho Yulia , Misikova Lenka Henao , Oh S. Paul , Franco Cláudio A. 
Published: August 2023

AbstractArteriovenous malformations (AVMs), a disorder characterized by direct shunts between arteries and veins, are associated with genetic mutations. However, the mechanisms leading to the transformation of a capillary into a shunt remain unclear and how shunts can be reverted into capillaries is poorly understood. Here, we report that oxygen-induced retinopathy (OIR) protocol leads to the consistent and stereotypical formation of AV shunts in non-genetically altered mice. OIR-induced AV shunts show all the canonical markers of AVMs. Genetic and pharmacological interventions demonstrated that changes in endothelial cell (EC) volume of venous origin (hypertrophic venous cells) are the initiating step promoting AV shunt formation, whilst EC proliferation or migration played minor roles. Inhibition of mTOR pathway prevents pathological increases in EC volume and significantly reduces the formation of AV shunts. Importantly, we demonstrate that ALK1 signaling cell-autonomously regulates EC volume, demonstrating that our discoveries link with hereditary hemorrhagic telangiectasia (HHT)-related AVMs. Finally, we demonstrate that a combination of EC volume control and EC migration is associated with the regression of AV shunts.We demonstrate that an increase in the EC volume is the key mechanism driving the initial stages of AV shunt formation, leading to asymmetric capillary diameters. Based on our results, we propose a coherent and unifying timeline leading to the fast conversion of a capillary vessel into an AV shunt. Our data advocates for further investigation into the mechanisms regulating EC volume in health and disease as a way to identify therapeutic approaches to prevent and revert AVMs.