bluuebunny/crossref_metadata_2025 huggingface dataset:
TIPE proteins control directed migration of human T cells by directing GPCR and lipid second messenger signaling
Authors: Yu Jiyeon , Zamani Ali , Goldsmith Jason R , Etwebi Zienab , Lee Chin Nien , Chen Youhai H , Sun Honghong
Published: November 2023

Tissue infiltration by circulating leukocytes via directed migration (also referred to as chemotaxis) is a common pathogenic mechanism of inflammatory diseases. G protein–coupled receptors (GPCRs) are essential for sensing chemokine gradients and directing the movement of leukocytes during immune responses. The tumor necrosis factor α-induced protein 8-like (TIPE or TNFAIP8L) family of proteins are newly described pilot proteins that control directed migration of murine leukocytes. However, how leukocytes integrate site-specific directional cues, such as chemokine gradients, and utilize GPCR and TIPE proteins to make directional decisions are not well understood. Using both gene knockdown and biochemical methods, we demonstrated here that 2 human TIPE family members, TNFAIP8 and TIPE2, were essential for directed migration of human CD4+ T cells. T cells deficient in both of these proteins completely lost their directionality. TNFAIP8 interacted with the Gαi subunit of heterotrimeric (α, β, γ) G proteins, whereas TIPE2 bound to PIP2 and PIP3 to spatiotemporally control immune cell migration. Using deletion and site-directed mutagenesis, we established that Gαi interacted with TNFAIP8 through its C-terminal amino acids, and that TIPE2 protein interacted with PIP2 and PIP3 through its positively charged amino acids on the α0 helix and at the grip-like entrance. We also discovered that TIPE protein membrane translocation (i.e. crucial for sensing chemokine gradients) was dependent on PIP2. Collectively, our work describes a new mechanistic paradigm for how human T cells integrate GPCR and phospholipid signaling pathways to control directed migration. These findings have implications for therapeutically targeting TIPE proteins in human inflammatory and autoimmune diseases.
Expression, clinicopathological significance, and prognostic potential of AMPK, p-AMPK, PGC-1α, and TFAM in astrocytomas
Authors: Wang Juan , Lou Lei , Li Dan , Wang Yuan , Jia Xin , Hao Xue , Liu Weina , Li Yuehong , Wu Wenxin , Hou Lianguo , Cui Jinfeng
Published: November 2023

AMP-activated protein kinase (AMPK) is a sensor of energy status that maintains cellular energy homeostasis. Activation of AMPK enhances the expression of proliferator-activated receptor γ coactivator 1α (PGC1-α) and subsequently activates mitochondrial transcription factor A (TFAM) to regulate mitochondrial oxidative respiratory function. The possible functions of AMPK, p-AMPK, PGC-1α, and TFAM and their interactions in astrocytomas are not known. Here, the levels, clinicopathological characteristics, and prognostic potential of AMPK, p-AMPK, PGC-1α, and TFAM expression levels in astrocytomas were evaluated. The results showed that levels of AMPK, p-AMPK, PGC-1α, and TFAM expression was increased in astrocytomas. Strong correlations were observed between AMPK, p-AMPK, PGC-1α, and TFAM expression in patients with astrocytomas. The analysis indicated that the levels of AMPK, p-AMPK, PGC-1α, and TFAM were associated with the survival. AMPK levels, tumor grade, and age were independent prognostic factors predicting poor outcomes in patients with astrocytoma. Together, these results indicate that these 4 targets may play a crucial role in the progression and prognosis of human astrocytomas and that AMPK may represent a potential therapeutic target.
International sanctions enacted against Russia as overriding mandatory rules—on which foot should international arbitrators stand?
Authors: Chevalier Maxime
Published: November 2023

Over the last decades, the role of international arbitrators has evolved from dealing with purely private interests to promoting the rule of law worldwide and safeguarding the interests of the international community. Following the armed conflict in Ukraine, a plurality of States has enacted international sanctions against Russia, which are currently impacting the performance of many international contracts. This article analyses the enforcement of international sanctions by international arbitrators as a matter of overriding mandatory public policy rules. This article also draws a new perspective on the subject, by analysing it from two different yet complementary approaches. First, because national courts have supervisory powers at the post-award stage, the reasoning of international arbitrators may depend on whether such international sanctions are regarded as public policy rules within relevant national legal orders. Secondly, because international arbitral tribunals have no forum, their decision regarding the enforcement of international sanctions will depend on the existing legal theories of international arbitration. After comparing the different results under the territorial, multilocal, and transnational approaches, the author advocates for the enforcement of international sanctions against Russia as part of transnational public policy rules.
A Feasibility Randomized Trial Evaluating Safe Peds: A Virtual Reality Training Program to Teach Children When to Cross Streets Safely
Authors: Morrongiello Barbara A , Corbett Michael , Dodd Belle , Zolis Caroline
Published: November 2023

Objective

Injury as pedestrians is a leading contributor to childhood deaths. This study evaluated the effectiveness of Safe Peds, a fully immersive virtual reality training program to teach children when to cross street safely, with the focus on a number of foundational skills and practicing these in traffic situations of varying complexity.

Methods

Children 7–10 years old were randomly assigned to a control (N = 31) or intervention (N = 26) group. Eligibility criteria included English speaking and typically developing. Testing took place on campus. All children completed pre- and post-testing measures, with those in the intervention group receiving training in between. Training comprised 1 session with 3 phases for a total of up to 1.5 hr and was tailored to each child’s performance over trials. On each trial, children decided when to cross and fully executed this crossing, with measures automatically taken by the system as they did so.

Results

Negative binomial regression and analysis of covariance tests were applied, predicting post-test scores while controlling for pre-test scores, age, and sex. The intervention was effective in improving children’s street crossing skills, including stopping and checking skills (stop at the curb, look left/right/left, check for traffic before crossing the yellow line), and choosing safe inter-vehicle gaps. Children in the control group did not show significant improvements in any crossing skills.

Conclusions

The Safe Peds program effectively teaches children skills to support their deciding when to safely cross in a variety of traffic situations. Implications for pedestrian injury are discussed.
Sacral metastases in a patient with BRAF V600E+ papillary thyroid carcinoma
Authors: Bhethanabotla Rohith M , Mohan Suresh , Lin Derrick , Shah Prerak
Published: November 2023

Lack of consensus exists on an algorithm to screen for synchronous distant metastases in patients presenting with papillary thyroid carcinoma (PTC). A 68-year-old male presented with a 3 cm supraclavicular neck mass. Computed tomography (CT) scan revealed a 1.3 cm left thyroid lobe nodule and 3 cm left level 3 and 4 lymphadenopathy. Ultrasound-guided fine needle aspiration was positive for PTC. Patient underwent total thyroidectomy and lymph node dissection with molecular testing confirming BRAF V600E+ PTC. Six weeks post-operatively, he developed left hip pain and numbness. Magnetic resonance imaging (MRI) revealed a large sacral mass and multiple bony lesions confirmed to be osseous metastases. Given the relatively rapid report of hip pain after surgery, metastases were likely synchronous at presentation and may have been detected with earlier suspicion. Further investigation is necessary to systematically stratify risk of synchronous distant metastases in patients with metastatic PTC.
Unilateral proptosis: a rare presentation of metastatic prostate cancer
Authors: Sharma Gaurav , Wanis Michael
Published: November 2023

Prostate adenocarcinomas with metastatic cranial involvement are rare, with signs and symptoms overlapping with those of the primary base of the skull tumour. The diagnosis was made following a biopsy of the suspected lesions that indicated the possibility of a prostatic primary malignancy based on immunohistochemistry using prostate-specific membrane antigen and subsequently confirmed histologically. We report an unusual case of a 52-year-old male who presented with unilateral proptosis and no prior urological history. Cranial, pulmonary, and thoracolumbar spinal metastases were identified with radiological imaging. We describe the diagnostic evaluation and treatment, as well as outline the rare nature of this case of cranial metastasis of prostate cancer.
Eviscerated liver: an extremely rare complication of abdominal wound dehiscense through a midline incision
Authors: Elbashier Mohanad , Rafei Ahmed , Abdulkarim Abdulwahab , Soud Mohamed , Musa Hassan , Taher Ali , Suliman Alsadig
Published: November 2023

Abdominal wound dehiscense, or burst abdomen, is a critical postoperative complication necessitating immediate intervention. We present an extremely rare case of left hepatic lobe evisceration through wound dehiscense in a 65-year-old female receiving palliative care for hypopharyngeal squamous cell carcinoma. The patient’s midline incision that was performed for feeding jejunostomy tube displayed liver protrusion on Day 14 postoperatively. Surgical exploration revealed a healthy liver, prompting reduction and secondary sutures to prevent complications. Abdominal wound dehiscense risk factors, including advanced age, poor nutrition, and medical illness, contribute to its occurrence. Although guidelines for liver evisceration management are lacking, our case emphasizes proper technique, wound care, and nutritional support to aid the healing process and to ensure a better outcome for the patients.
Emergence of blaNDM-5-harbouring Escherichia coli ST617 in refugee and host communities and their environment
Authors: Daaboul Dina , Kassem Issmat I , El Omari Khaled , Hamze Monzer , Daboussi Fouad , Oueslati Saoussen , Naas Thierry , Osman Marwan
Published: November 2023

Antimicrobial resistance disproportionately affects displaced and vulnerable populations. Here, we performed an in-depth investigation of blaNDM-5-harbouring Escherichia coli ST617 isolated from disenfranchised Lebanese patients, Syrian refugees, and livestock and the environment of refugee camps. We highlight the need for proactive One Health strategies to combat antimicrobial resistance in vulnerable populations.
Diagnostic challenges and antibody kinetics in a paediatric traveller with scrub typhus
Authors: Looareesuwan Panita , Aiemjoy Kristen , Charoensakulchai Sakarn , Thaipadungpanit Janjira , Wongsantichon Jantana , Tanganuchitcharnchai Ampai , Rungrojn Artharee , Blacksell Stuart D , Matsee Wasin
Published: November 2023

Diagnosing scrub typhus in travellers is challenging due to symptom similarities with other travel-related illnesses and limited early diagnostic tools. We present a distinctive case of scrub typhus in a child traveller, providing a comprehensive account of the case, the diagnostic challenges encountered, laboratory findings and the dynamics of antibodies.
Persulfidation of plant and bacteroid proteins is involved in legume nodule development and senescence
Authors: Matamoros Manuel A , Romero Luis C , Tian Tao , Román Ángela , Duanmu Deqiang , Becana Manuel
Published: November 2023

Legumes establish symbiosis with rhizobia, forming nitrogen-fixing nodules. The central role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in nodule biology has been clearly established. Recently, hydrogen sulfide (H2S) and other reactive sulfur species (RSS) have emerged as novel signaling molecules in animals and plants. A major mechanism by which ROS, RNS, and RSS fulfil their signaling role is the post-translational modification of proteins. To identify possible functions of H2S in nodule development and senescence, we used the tag-switch method to quantify changes in the persulfidation profile of common bean (Phaseolus vulgaris) nodules at different developmental stages. Proteomic analyses indicate that persulfidation plays a regulatory role in plant and bacteroid metabolism and senescence. The effect of a H2S donor on nodule functioning and on several proteins involved in ROS and RNS homeostasis was also investigated. Our results using recombinant proteins and nodulated plants support a crosstalk among H2S, ROS, and RNS, a protective function of persulfidation on redox-sensitive enzymes, and a beneficial effect of H2S on symbiotic nitrogen fixation. We conclude that the general decrease of persulfidation levels observed in plant proteins of aging nodules is one of the mechanisms that disrupt redox homeostasis leading to senescence.
Leaf abaxial immunity to powdery mildew in Arabidopsis is conferred by multiple defense mechanisms
Authors: Wu Ying , Sexton W Kyle , Zhang Qiong , Bloodgood David , Wu Yan , Hooks Caroline , Coker Frank , Vasquez Andrea , Wei Cheng-I , Xiao Shunyuan
Published: November 2023

Powdery mildew fungi are obligate biotrophic pathogens that only invade plant epidermal cells. There are two epidermal surfaces in every plant leaf: the adaxial (upper) side and the abaxial (lower) side. While both leaf surfaces can be susceptible to adapted powdery mildew fungi in many plant species, there have been observations of leaf abaxial immunity in some plant species including Arabidopsis. The genetic basis of such leaf abaxial immunity remains unknown. In this study, we tested a series of Arabidopsis mutants defective in one or more known defense pathways with the adapted powdery mildew isolate Golovinomyces cichoracearum UCSC1. We found that leaf abaxial immunity was significantly compromised in mutants impaired for both the EDS1/PAD4- and PEN2/PEN3-dependent defenses. Consistently, expression of EDS1–yellow fluorescent protein and PEN2–green fluorescent protein fusions from their respective native promoters in the respective eds1-2 and pen2-1 mutant backgrounds was higher in the abaxial epidermal cells than in the adaxial epidermal cells. Altogether, our results indicate that leaf abaxial immunity against powdery mildew in Arabidopsis is at least partially due to enhanced EDS1/PAD4- and PEN2/PEN3-dependent defenses. Such transcriptionally pre-programmed defense mechanisms may underlie leaf abaxial immunity in other plant species such as hemp and may be exploited for engineering adaxial immunity against powdery mildew fungi in crop plants.
A group VIIIa ethylene-responsive factor, CmERF4, negatively regulates waterlogging tolerance in chrysanthemum
Authors: Li Chuanwei , Wang Likai , Su Jiangshuo , Li Wenjie , Tang Yun , Zhao Nan , Lou La , Ou Xiaoli , Jia Diwen , Jiang Jiafu , Chen Sumei , Chen Fadi
Published: November 2023

Ethylene-responsive factors (ERF) play an important role in plant responses to waterlogging stress. However, the function and mechanism of action of ERFVIII in response to waterlogging stress remain poorly understood. In this study, we found that expression of the ERF VIIIa gene CmERF4 in chrysanthemum was induced by waterlogging stress. CmERF4 localized to the nucleus when expressed in tobacco leaves. Yeast two-hybrid and luciferase assays showed that CmERF4 is a transcriptional inhibitor. CmERF4 overexpression in chrysanthemum reduced plant waterlogging tolerance, whereas overexpression of the chimeric activator CmERF4-VP64 reversed its transcriptional activity, promoting higher waterlogging tolerance than that observed in wild-type plants, indicating that CmERF4 negatively regulates waterlogging tolerance. Transcriptome profiling showed that energy metabolism and reactive oxygen species (ROS) pathway-associated genes were differentially expressed between CmERF4-VP64 and wild-type plants. RT–qPCR analysis of selected energy metabolism and reactive oxygen species-related genes showed that the gene expression patterns were consistent with the expression levels obtained from RNA-seq analysis. Overall, we identified new functions of CmERF4 in negatively regulating chrysanthemum waterlogging tolerance by modulating energy metabolism and ROS pathway genes.
Cloud–cloud collision in S235: triggered the formation of high-mass stars and young star clusters
Authors: Chen En , Gao Yu , Zhang Shiyu , Chen Xuepeng , Fang Min , He Qianru , Jiang Xue-Jian , Sun Yan , Wang Xiao-Long , Ma Hongjun
Published: November 2023

We present the analysis of cloud–cloud collision (CCC) process in the Galactic molecular complex S235. Our new CO observations performed with the PMO-13.7 m telescope reveal two molecular clouds, namely the S235-Main and the S235-ABC, with ∼4 km s−1 velocity separation. The bridge feature, the possible colliding interface and the complementary distribution of the two clouds are significant observational signatures of cloud–cloud collision in S235. The most direct evidence of cloud–cloud collision process in S235 is that the S235-Main (in a distance of 1547$^{+44}_{-43}$ pc) and S235-ABC (1567$^{+33}_{-39}$ pc) meet at almost the same position (within 1σ error range) at a supersonic relative speed. We identified ten 13CO clumps from PMO-13.7 m observations, 22 dust cores from the archival SCUBA-2 data, and 550 YSOs from NIR–MIR data. 63 per cent of total YSOs are clustering in seven MST groups (M1−M7). The tight association between the YSO groups (M1 $\&$ M7) and the bridge feature suggests that the CCC process triggers star formation there. The collisional impact subregion (the South) shows 3 ∼ 5 times higher CFE and SFE (average value of 12.3 and 10.6 per cent, respectively) than the non-collisional impact subregion (2.4 and 2.6 per cent, respectively), suggesting that the CCC process may have enhanced the CFE and SFE of the clouds compared to those without collision influence.
Unsupervised machine learning models reveal predictive clinical markers of glioblastoma patient survival using white blood cell counts prior to initiating chemoradiation
Authors: Wang Wesley , Kumm Zeynep Temerit , Ho Cindy , Zanesco-Fontes Ideli , Texiera Gustavo , Reis Rui Manuel , Martinetto Horacio , Khan Javaria , McCandless Martin G , Baker Katherine E , Anderson Mark D , Chohan Muhammad Omar , Beyer Sasha , Elder J Brad , Giglio Pierre , Otero José Javier
Published: November 2023

Background

Glioblastoma is a malignant brain tumor requiring careful clinical monitoring even after primary management. Personalized medicine has suggested the use of various molecular biomarkers as predictors of patient prognosis or factors utilized for clinical decision-making. However, the accessibility of such molecular testing poses a constraint for various institutes requiring identification of low-cost predictive biomarkers to ensure equitable care.

Methods

We collected retrospective data from patients seen at Ohio State University, University of Mississippi, Barretos Cancer Hospital (Brazil), and FLENI (Argentina) who were managed for glioblastoma—amounting to 581 patient records documented using REDCap. Patients were evaluated using an unsupervised machine learning approach comprised of dimensionality reduction and eigenvector analysis to visualize the inter-relationship of collected clinical features.

Results

We discovered that the serum white blood cell (WBC) count of a patient during baseline planning for treatment was predictive of overall survival with an over 6-month median survival difference between the upper and lower quartiles of WBC count. By utilizing an objective PD-L1 immunohistochemistry quantification algorithm, we were further able to identify an increase in PD-L1 expression in glioblastoma patients with high serum WBC counts.

Conclusions

These findings suggest that in a subset of glioblastoma patients the incorporation of WBC count and PD-L1 expression in the brain tumor biopsy as simple biomarkers predicting glioblastoma patient survival. Moreover, machine learning models allow the distillation of complex clinical data sets to uncover novel and meaningful clinical relationships.
A comparative study of microsurgery and gamma knife radiosurgery in vestibular schwannoma evaluating tumor control and functional outcome
Authors: Tatagiba Marcos , Wang Sophie S , Rizk Ahmed , Ebner Florian , van Eck Albertus T C J , Naros Georgios , Horstmann Gerhard
Published: November 2023

Background

Both stereotactic radiosurgery (SRS) and microsurgical resection (SURGERY) are available as treatment options for sporadic vestibular schwannoma (VS). There are very few direct comparative studies comparing both treatment modalities in large cohorts allowing detailed subgroup analysis. This present study aimed to compare the nuances in the treatment of VS by SURGERY and SRS in 2 highly specialized neurosurgical centers.

Methods

This is a retrospective bicentric cohort study. Data from patients treated between 2005 and 2011 were collected retrospectively. Recurrence-free survival (RFS) was assessed radiographically by contrast-enhanced magnetic resonance imaging.

Results

The study population included N = 901 patients with a mean follow-up of 7 years. Overall, the incidence of recurrence was 7% after SURGERY, and 11% after SRS with superior tumor control in SURGERY in the Kaplan–Meier-analysis (P = 0.031). In small tumors (Koos I and II), tumor control was equivalent in both treatment arms. In large VS (Koos III and IV), however, RFS was superior in SURGERY. The extent of resection correlated with RFS (P < .001). Facial and hearing deterioration was similar in both treatment arms in small VS, but more pronounced in SURGERY of large VS. Tinnitus, vertigo, imbalance, and trigeminal symptoms were more often improved by SURGERY than SRS.

Conclusions

SRS can achieve similar tumor control compared to SURGERY in smaller VS (Koos I and II)—with similar postinterventional morbidities. In large VS (Koos III and IV), long-term tumor control of SRS is inferior to SURGERY. Based on these results, we suggest that if combination therapy is chosen, the residual tumor should not exceed the size of Koos II.
Effects of Pictorial Health Warning Labels on Intention to Quit Waterpipe in Lebanon: A Mediation Analysis
Authors: Jebai Rime , Asfar Taghrid , Cano Miguel Ángel , Nakkash Rima , Schmidt Michael , Wu Wensong , Bursac Zoran , Maziak Wasim
Published: November 2023

Introduction

Pictorial health warning labels (HWLs) on waterpipe (WP) tobacco packages represent a better strategy for communicating the health risks associated with WP use and promoting quit intention than text-only. However, the mechanism by which these warnings lead to higher intentions to quit remains unknown.

Aims and Methods

This study explores how pictorial warnings versus text-only induces higher quit intention among a sample of young adult WP smokers in Lebanon. An online randomized cross-over experimental study was conducted in August 2021 among 276 young adult WP smokers who were exposed to two conditions: pictorial HWLs and text-only warnings on WP tobacco packages in random order. After each image, participants completed post-exposure assessments of health communication outcomes (eg, attention and negative affect). Using serial and parallel mediation analysis, we examined the role of attention, negative affect, cognitive elaboration, and perceived harm in mediating the relationship between exposure to HWLs and intention to quit.

Results

Using serial mediation, exposure to pictorial warnings versus text-only was found to affect intention to quit through the following pathways: attention and negative affect, which accounted for 17.28% of the total effect, and through negative affect and cognitive elaboration, which accounted for 21.53% of the total effect. Results of parallel mediation showed that the indirect effect pathways via negative affect (β = 0.063; [95% bootstrap CI = 0.004 to 0.149]) and cognitive elaboration (0.047; [0.001 to 0.114]) were statistically significant.

Conclusions

The findings call on designing and implementing attention-grabbing, emotionally evocative, and cognitively persuasive pictorial warnings in Lebanon and other countries to curb WP tobacco smoking.

Implications

This is among the first experimental studies looking at multiple mediators underlying the effect of exposure to pictorial HWLs on intention to quit in a sample of current WP smokers in Lebanon. The findings showed that using attention-grabbing, emotionally evocative, and persuasive pictures with a clear textual warning is crucial to maximizing the impact of implementing WP-HWLs regulations in Lebanon and other countries to curb WP tobacco smoking.
Experimental analysis of development, lipid accumulation and gene expression in a high-latitude marine copepod
Authors: Roncalli Vittoria , Block Lauren N , Niestroy Jeanette L , Cieslak Matthew C , Castelfranco Ann M , Hartline Daniel K , Lenz Petra H
Published: November 2023

The high-latitude copepod Neocalanus flemingeri exploits the spring phytoplankton bloom to accumulate lipids for survival during food-limited periods and to fuel reproduction. At some point during development, lipid-accumulation ends and pre-adults molt into adults, descend to depth and enter a state of dormancy termed "diapause." How and when they determine to make this transition is still unresolved. According to one hypothesis, the trigger is their attaining a threshold amount of "lipid fullness." Alternatively, they might follow a genetic program, entering diapause within a narrow developmental window. To better understand the decision, a 5-week laboratory experiment was conducted to assess the effect of food quantity and type on lipid accumulation, biomass and gene expression in N. flemingeri copepodite stage CV. In fed individuals, the initial rate of lipid accumulation slowed by week 5, as a portion of CVs began to molt into adults. While changes in gene expression common to all fed individuals between weeks 1 and 3 were consistent with a developmental program, the duration of the CV stage was variable. Unfed individuals maintained lipid stores initially, suggesting physiological acclimatization to conserve energy. A comparison with gene expression profiles of field-collected individuals suggests similar responses to resources in the environment.
Trade-offs between cold protection and air pollution–induced mortality of China's heating policy
Authors: Zhang Haofan , He Pan , Liu Linxin , Dai Hui , Zhao Bin , Zeng Yi , Bi Jun , Liu Miaomiao , Ji John S
Published: November 2023

The winter heating policy in northern China was designed to safeguard households from the harsh subfreezing temperatures. However, it has inadvertently resulted in seasonal spikes in air pollution levels because of the reliance on coal as an energy source. While the loss of life years attributable to mortality from air pollution caused by winter heating has been estimated, the beneficial effect of protection from cold temperatures has not been assessed, primarily due to a lack of individual-level data linking these variables. Our study aims to address this research gap. We provide individual-level empirical evidence that quantifies the impact of protection from cold temperatures and air pollution on mortality, studying 5,334 older adults living around the Huai River during the period between 2000 and 2018. Our adjusted Cox-proportional hazard models show that winter heating was associated with a 22% lower mortality rate (95% CI: 16–28%). Individuals residing in areas without access to winter heating are subjected to heightened mortality risks during periods of cold temperatures. The protective effect is offset by a 27.8% rise attributed to elevated PM2.5 levels. Our results imply that the equilibrium between the effects of these two factors is achieved when PM2.5 concentration exceeds 24.3 µg/m3 (95% CI: 18.4–30.2). Our research suggests that while the existing winter heating policy significantly mitigates winter mortality by lessening the detrimental effects of cold temperatures, future air pollution reduction could provide further health benefits.
ALCON EYE CARE UK LTD v AMO DEVELOPMENT, LLC
Authors:   Patents Court
Published: November 2023

H1 Patents—European patents—Revocation—Ophthalmic surgery—Cataract surgery—Validity—Characteristics and experience of the skilled person—Interaction between skilled team members—Common general knowledge—Negative or intermediate common general knowledge—Obviousness—Hindsight—Insufficiency—Evidence—Expert witnesses—Case management
Specificity in the processing of a subject’s own name
Authors: Bao Han , Xie Musi , Huang Ying , Liu Yutong , Lan Chuyi , Lin Zhiwei , Wang Yuzhi , Qin Pengmin
Published: November 2023

Subject’s own name (SON) is widely used in both daily life and the clinic. Event-related potential (ERP)-based studies have previously detected several ERP components related to SON processing; however, as most of these studies used SON as a deviant stimulus, it was not possible to determine whether these components were SON-specific. To identify SON-specific ERP components, we adopted a passive listening task with EEG data recording involving 25 subjects. The auditory stimuli were a SON, a friend’s name (FN), an unfamiliar name (UN) selected from other subjects’ names and seven different unfamiliar names (DUNs). The experimental settings included Equal-probabilistic, Frequent-SON, Frequent-FN and Frequent-UN conditions. The results showed that SON consistently evoked a frontocentral SON-related negativity (SRN) within 210–350 ms under all conditions, which was not detected with the other names. Meanwhile, a late positive potential evoked by SON was found to be affected by stimulus probability, showing no significant difference between the SON and the other names in the Frequent-SON condition, or between the SON and a FN in the Frequent-UN condition. Taken together, our findings indicated that the SRN was a SON-specific ERP component, suggesting that distinct neural mechanism underly the processing of a SON.
Bridging conflicting frames in policies for digital transformation
Authors: Coco Nunzia , Colapinto Cinzia , Finotto Vladi
Published: November 2023

Despite several policies aimed at igniting digital transformation, many regions lag behind. We investigate this discrepancy by postulating that the political consensus on accelerating Industry 4.0 adoption among micro-, small- and mid-sized enterprises (MSMEs) needs to consider the heterogeneity of entrepreneurial and social fabrics. Best practices in policy-making exist, but their deployment requires adaptations. The present paper delves into such adaptations and on the mechanics behind how a ‘model’ is modified locally. We do so by illustrating the results of action research on a regional policy initiative. Our findings point to one important set of factors and mechanisms conducive to the adaptation of a policy model to the peculiarities of a locale via the alignment of different cognitive frames: co-design processes. We elaborate on the role of different actors, the relevance of ‘hybrid’ actors, and the nature of universities as platforms
Hyperbaric oxygen therapy as a treatment for erectile dysfunction: a meta-analysis
Authors: Saffati Gal , Naeem Taher , Guhan Maya , Abello Alejandro , Hinojosa-Gonzalez David Eugenio , Kaaki Basil , Stocks Blair T , Lipshultz Larry I , Khera Mohit
Published: November 2023

Introduction

Hyperbaric oxygen therapy (HBOT) is a medical treatment in which the patient is exposed to 100% oxygen at a higher than atmospheric pressure. Over the past few decades, HBOT has been used to treat a variety of medical conditions. In recent times, there has been a rising curiosity regarding the potential therapeutic benefits of HBOT in the treatment of erectile dysfunction (ED).

Aims

The study sought to review and meta-analyze available data regarding the use of HBOT for ED, including its potential mechanisms of action and effectiveness.

Methods

We included only articles that evaluated the impact of HBOT on ED symptoms using the International Index of Erectile Function score. Prospective nonrandomized studies or randomized controlled clinical trials were included. Data extraction was performed in duplicate. Data analysis was conducted using Review Manager 5.41, and the presence of heterogeneity between studies was evaluated. The results were presented as the mean difference (MD) with 95% confidence interval (CI).

Results

A total of 5 studies that reported outcomes using the International Index of Erectile Function scores were included in this analysis. In patients with post–robotic-assisted laparoscopic prostatectomy–induced ED, the analysis showed a significant MD of −4.13 (95% CI, −6.08 to −2.18; P < .0001) in favor of the control group. Conversely, patients who received HBOT for reasons other than ED exhibited an MD of 4.58 (95% CI, 2.63 to 6.52; P < .00001). In the group that received HBOT for pure vasculogenic ED, the MD was 10.50 (95% CI, 9.92 to 11.08) in favor of HBOT. A meta-analysis of these data revealed a nonsignificant difference in erectile function scores, with an MD of 3.86 (95% CI, −2.13 to 9.86; P = .21).

Conclusion

The use of HBOT in the treatment of ED appears to be a promising approach. While further research is needed to establish the efficacy and long-term effects of this treatment, preliminary studies have shown encouraging results in terms of improving erectile function in men with vasculogenic ED.
Advancing reproducibility can ease the ‘hard truths’ of synthetic biology
Authors: Lux Matthew W , Strychalski Elizabeth A , Vora Gary J
Published: November 2023

Reproducibility has been identified as an outstanding challenge in science, and the field of synthetic biology is no exception. Meeting this challenge is critical to allow the transformative technological capabilities emerging from this field to reach their full potential to benefit the society. We discuss the current state of reproducibility in synthetic biology and how improvements can address some of the central shortcomings in the field. We argue that the successful adoption of reproducibility as a routine aspect of research and development requires commitment spanning researchers and relevant institutions via education, incentivization and investment in related infrastructure. The urgency of this topic pervades synthetic biology as it strives to advance fundamental insights and unlock new capabilities for safe, secure and scalable applications of biotechnology.

Graphical Abstract
Discovery and genome characterization of six new orthoparamyxoviruses in small Belgian mammals
Authors: Horemans Marie , Van Bets Jessica , Joly Maes Tibe , Maes Piet , Vanmechelen Bert
Published: November 2023

In the future, zoonotic spillover events are expected to occur more frequently. Consequences of such events have clearly been demonstrated by recent outbreaks of monkeypox, Ebola virus, and the well-known severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Virus discovery has proven to be an important tool in the preparation against viral outbreaks, generating data concerning the diversity, quantity, and ecology of the vertebrate virome. Orthoparamyxoviruses, a subfamily within the Paramyxoviridae, are important biosurveillance targets, since they include several known animal, human, and zoonotic pathogens such as Nipah virus, measles virus, and Hendra virus. During this study, 127 bat samples, thirty-four rodent samples, and seventeen shrew samples originating from Belgium were screened for orthoparamyxovirus presence using nested reverse transcription–polymerase chain reaction assays and nanopore sequencing. We present here the complete genomes of six putative new viral species, belonging to the genera Jeilongvirus and Henipavirus. Characterization of these genomes revealed significant differences in gene composition and organization, both within viruses of the same genus and between viruses of different genera. Remarkably, a previously undetected gene coding for a protein of unknown function was identified in the genome of a putative new Henipavirus. Additionally, phylogenetic analysis of jeilongviruses and henipaviruses reveals a division of both genera into two clades, one consisting of bat-borne viruses and the other consisting of rodent- and shrew-borne viruses, elucidating the need for proper reclassification.
Germline-targeting SOSIP trimer immunization elicits precursor CD4 binding-site targeting broadly neutralizing antibodies in infant macaques
Authors: Nelson Ashley N. , Shen Xiaoying , Vekatayogi Sravani , Zhang Shiyu , Ozorowski Gabriel , Dennis Maria , Sewall Leigh M. , Milligan Emma , Davis Dominique , Cross Kaitlyn A. , Chen Yue , van Schooten Jelle , Eudailey Joshua , Isaac John , Memon Saad , Weinbaum Carolyn , Stanfield-Oakley Sherry , Byrd Alliyah , Chutkan Suni , Berendam Stella , Cronin Kenneth , Yasmeen Anila , Alam S. Munir , LaBranche Celia C. , Rogers Kenneth , Shirreff Lisa , Cupo Albert , Derking Ronald , Villinger Francois , Klasse Per Johan , Ferrari Guido , Williams Wilton B. , Hudgens Michael G. , Ward Andrew B. , Montefiori David C. , Van Rompay Koen K.A. , Wiehe Kevin , Moore John P. , Sanders Rogier W. , De Paris Kristina , Permar Sallie R.
Published: November 2023

A vaccine that can achieve protective immunity prior to sexual debut is critical to prevent the estimated 410,000 new HIV infections that occur yearly in adolescents. As children living with HIV can make broadly neutralizing antibody (bnAb) responses in plasma at a faster rate than adults, early childhood is an opportune window for implementation of a multi-dose HIV immunization strategy to elicit protective immunity prior to adolescence. Therefore, the goal of our study was to assess the ability of a B cell lineage-designed HIV envelope SOSIP to induce bnAbs in early life. Infant rhesus macaques (RMs) received either BG505 SOSIP or the germline-targeting BG505 GT1.1 SOSIP (n=5/group) with the 3M-052-SE adjuvant at 0, 6, and 12 weeks of age. All infant RMs were then boosted with the BG505 SOSIP at weeks 26, 52 and 78, mimicking a pediatric immunization schedule of multiple vaccine boosts within the first two years of life. Both immunization strategies induced durable, high magnitude binding antibodies and plasma autologous virus neutralization that primarily targeted the CD4-binding site (CD4bs) or C3/465 epitope. Notably, three BG505 GT1.1-immunized infants exhibited a plasma HIV neutralization signature reflective of VRC01-like CD4bs bnAb precursor development and heterologous virus neutralization. Finally, infant RMs developed precursor bnAb responses at a similar frequency to that of adult RMs receiving a similar immunization strategy. Thus, a multi-dose immunization regimen with bnAb lineage designed SOSIPs is a promising strategy for inducing protective HIV bnAb responses in childhood prior to adolescence when sexual HIV exposure risk begins.
Human cortical high-gamma power relates to movement speed and is disproportionately reduced after stroke
Authors: Haverland Benjamin , Timmsen Lena S. , Wolf Silke , Stagg Charlotte J. , Frontzkowski Lukas , Oostenveld Robert , Feldheim Jan , Higgen Focko L. , Gerloff Christian , Schulz Robert , Schneider Till R. , Schwab Bettina C. , Quandt Fanny
Published: November 2023

Motor cortical high-gamma oscillations (60 to 90 Hz) occur at the onset of movement and are spatially focused over the contralateral primary motor cortex. Although high-gamma oscillations are widely recognized for their significance in human motor control, their precise function on a cortical level remains elusive. Importantly, their relevance in human stroke pathophysiology is unknown. Understanding the neurophysiological processes of motor coding could be an important step in improving motor recovery after stroke. We recorded magnetoencephalography data during a thumb movement speed task in 14 chronic stroke survivors, 15 age-matched control participants and 29 healthy young participants. Motor cortical high-gamma oscillations showed a strong relation withmovement speedas trials with highermovement speedwere associated with greater high-gamma power. Stroke survivors showed reduced cortical high-gamma power, surpassing the effect attributable to decreasedmovement speedin these participants. Even though motor skill acquisition was evident in all groups, it was not linked to high-gamma power. Our study is, to our knowledge, the first to quantify high-gamma oscillations after stroke, revealing a reduction in movement-related high-gamma power. Moreover, we provide strong evidence for a pivotal role of motor cortical high-gamma oscillations in encodingmovement speed.
Stress granule formation helps to mitigate neurodegeneration
Authors: Glineburg M. Rebecca , Yildirim Evrim , Gomez Nicolas , Li Xingli , Pak Jaclyn , Altheim Christopher , Waksmacki Jacob , McInerney Gerald , Barmada Sami J. , Todd Peter K.
Published: November 2023

Cellular stress pathways that inhibit translation initiation lead to transient formation of cytoplasmic RNA/protein complexes known as stress granules. Many of the proteins found within stress granules and the dynamics of stress granule formation and dissolution are implicated in neurodegenerative disease. Whether stress granule formation is protective or harmful in neurodegenerative conditions is not known. To address this, we took advantage of the alphavirus protein nsP3, which selectively binds dimers of the central stress granule nucleator protein G3BP (rininDrosophila) and markedly reduces stress granule formation without directly impacting the protein translational inhibitory pathways that trigger stress granule formation. InDrosophilaand rodent neurons, reducing stress granule formation with nsP3 had modest impacts on lifespan even in the setting of serial stress pathway induction. In contrast, reducing stress granule formation in models of ataxia, amyotrophic lateral sclerosis and frontotemporal dementia largely exacerbated disease phenotypes. These data support a model whereby stress granules mitigate, rather than promote, neurodegenerative cascades.
2D and 3D multiplexed subcellular profiling of nuclear instability in human cancer
Authors: Coy Shannon , Cheng Brian , Lee Jong Suk , Rashid Rumana , Browning Lindsay , Xu Yilin , Chakrabarty Sankha S. , Yapp Clarence , Chan Sabrina , Tefft Juliann B. , Scott Emily , Spektor Alexander , Ligon Keith L. , Baker Gregory J. , Pellman David , Sorger Peter K. , Santagata Sandro
Published: November 2023

Nuclear atypia, including altered nuclear size, contour, and chromatin organization, is ubiquitous in cancer cells. Atypical primary nuclei and micronuclei can rupture during interphase; however, the frequency, causes, and consequences of nuclear rupture are unknown in most cancers. We demonstrate that nuclear envelope rupture is surprisingly common in many human cancers, particularly glioblastoma. Using highly-multiplexed 2D and super-resolution 3D-imaging of glioblastoma tissues and patient-derived xenografts and cells, we link primary nuclear rupture with reduced lamin A/C and micronuclear rupture with reduced lamin B1. Moreover, ruptured glioblastoma cells activate cGAS-STING-signaling involved in innate immunity. We observe that local patterning of cell states influences tumor spatial organization and is linked to both lamin expression and rupture frequency, with neural-progenitor-cell-like states exhibiting the lowest lamin A/C levels and greatest susceptibility to primary nuclear rupture. Our study reveals that nuclear instability is a core feature of cancer, and links nuclear integrity, cell state, and immune signaling.
Predator Odor Stressor, 2,3,5-trimethyl-3-thiazoline (TMT): Assessment of stress reactive behaviors during an animal model of traumatic stress in rats
Authors: Ornelas Laura C. , Besheer Joyce
Published: November 2023

Animal models utilizing predator odor stress are important in understanding implications for post-traumatic stress disorder. 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) has been used to measure stress reactive behaviors during TMT exposure, indicative of stress coping behaviors. In addition, long-term consequences of stress including contextual-induced stress memory, anxiety-like and hyperarousal behaviors, and subsequent increases in alcohol self- administration can also be examined after TMT exposure.

In this article, we describe the TMT exposure protocol used in our lab and how we measure different stress-reactive behaviors that rats engage in during the TMT exposure. Rats are placed in Plexiglas chambers that contains white bedding on the bottom of the chamber and a metal basket in the top right corner that contains a filter paper on which 10 µL of TMT is pipetted onto. During the 10 min exposure, rats can move around the chamber freely. Exposures are recorded by a video camera for later analysis.

During TMT exposure, rats engage in a variety of stress-reactive behaviors, including digging and immobility behavior. These are two distinctly different types of stress-induced behavioral coping strategies to measure individual differences in stress responsivity. To examine individual differences, we group rats into TMT-subgroups based on time spent engaging in digging or immobility behavior. We calculate a digging/immobility ratio score in which we divide the total time spent digging by the total time spent immobile. A cut-off strategy is used such that rats with a criterion ratio score below 1.0 are classified as TMT-1 (i.e., low digging/high immobility; greater passive coping) and rats with a ratio score above 1.0 are classified as TMT-2 (i.e., high digging/low immobility; greater active coping).

In the present paper, we provide a detailed description of the TMT exposure protocol and step- by-step process in evaluation of stress-reactive behaviors.

Basic Protocol 1:Predator Odor Stressor Exposure using TMT

Basic Protocol 2:Description of Stress-Reactive Behaviors during TMT Exposure and Formation of TMT-subgroups
Progressive degeneration in a newDrosophilamodel of Spinocerebellar Ataxia type 7
Authors: Sujkowski Alyson L. , Ranxhi Bedri , Prifti Matthew V. , Alam Nadir , Todi Sokol V. , Tsou Wei-Ling
Published: November 2023

Spinocerebellar ataxia type 7 (SCA7) is a progressive neurodegenerative disorder resulting from abnormal expansion of polyglutamine (polyQ) in its disease protein, ataxin-7 (ATXN7). ATXN7 is part of Spt-Ada-Gcn5 acetyltransferase (SAGA), an evolutionarily conserved transcriptional coactivation complex with critical roles in chromatin remodeling, cell signaling, neurodifferentiation, mitochondrial health and autophagy. SCA7 is dominantly inherited and characterized by genetic anticipation and high repeat-length instability. Patients with SCA7 experience progressive ataxia, atrophy, spasticity, and blindness. There is currently no cure for SCA7, and therapies are aimed at alleviating symptoms to increase quality of life. Here, we report novelDrosophilalines of SCA7 with polyQ repeats in wild-type and human disease patient range. We find that ATXN7 expression has age- and polyQ repeat length-dependent reduction in survival and retinal instability, concomitant with increased ATXN7 protein aggregation. These new lines will provide important insight on disease progression that can be used in the future to identify therapeutic targets for SCA7 patients.