bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tilt-induced polar order and topological defects in growing bacterial populations
Authors: Shimaya Takuro , Takeuchi Kazumasa A 
Published: December 2022

AbstractRod-shaped bacteria, such as Escherichia coli, commonly live forming mounded colonies. They initially grow two-dimensionally on a surface and finally achieve three-dimensional growth. While it was recently reported that three-dimensional growth is promoted by topological defects of winding number +1/2 in populations of motile bacteria, how cellular alignment plays a role in nonmotile cases is largely unknown. Here, we investigate the relevance of topological defects in colony formation processes of nonmotile E. coli populations, and found that both ±1/2 topological defects contribute to the three-dimensional growth. Analyzing the cell flow in the bottom layer of the colony, we observe that +1/2 defects attract cells and −1/2 defects repel cells, in agreement with previous studies on motile cells, in the initial stage of the colony growth. However, later, cells gradually flow toward −1/2 defects as well, exhibiting a sharp contrast to the existing knowledge. By investigating three-dimensional cell orientations by confocal microscopy, we find that vertical tilting of cells is promoted near the defects. Crucially, this leads to the emergence of a polar order in the otherwise nematic two-dimensional cell orientation. We extend the theory of active nematics by incorporating this polar order and the vertical tilting, which successfully explains the influx toward −1/2 defects in terms of a polarity-induced force. Our work reveals that three-dimensional cell orientations may result in qualitative changes in properties of active nematics, especially those of topological defects, which may be generically relevant in active matter systems driven by cellular growth instead of self-propulsion.
Metaverse as a new place for online mental health services in the post-COVID-19 era: Is it a challenge or an opportunity?
Authors: Situmorang Dominikus David Biondi 
Published: December 2022

Abstract
In this article, the author describes the challenges and opportunities of metaverse’s presence in the world for online mental health services. Aside from that, the author provides insight that metaverse can become a new place that is more comfortable and enjoyable for everyone who can relish the online mental health meetings with a new atmosphere and sensation, especially in the post-COVID-19 era.
Clinically meaningful changes in efficacy outcomes in chronic rhinosinusitis with nasal polyposis
Authors: Mitchell Margaret B. , Workman Alan D. , Lee Stella E. 
Published: December 2022

Purpose of review
Chronic rhinosinusitis with nasal polyps (CRSwNP) carries a high disease burden, and many studies have been done investigating the efficacy of various medical and surgical therapies. However, outcome metrics have varied across these studies, making it difficult to compare therapeutic efficacy on a large scale. In this article, we discuss various outcome metrics used across prior studies as well as the relationship between these measures.

Recent findings
Outcome metrics in CRSwNP studies include both clinically assessed and patient-reported outcome measures (PROMs). The former includes olfaction testing, scoring systems based on imaging and endoscopic evaluation, and histopathological and immunohistochemical evaluation of sinus tissue, and the latter includes quality-of-life instruments, symptom severity scales, and disease-control instruments. Recent studies evaluating the efficacy of new biologics have used a combination of both types of metrics.

Summary
Both clinical metrics and patient-reported outcomes provide utility in evaluating disease severity and control in patients with CRSwNP, although there are nuances when comparing therapies in this population as patients with CRSwNP are heterogeneous and may have symptoms across several domains. However, PROMs in conjunction with clinical metrics provide useful information to assess patient symptoms and response to interventions.
Gene therapy for inborn error of immunity – current status and future perspectives
Authors: Mudde Anne , Booth Claire 
Published: December 2022

Purpose of review
Development of hematopoietic stem cell (HSC) gene therapy (GT) for inborn errors of immunity (IEIs) continues to progress rapidly. Although more patients are being treated with HSC GT based on viral vector mediated gene addition, gene editing techniques provide a promising new approach, in which transgene expression remains under the control of endogenous regulatory elements.

Recent findings
Many gene therapy clinical trials are being conducted and evidence showing that HSC GT through viral vector mediated gene addition is a successful and safe curative treatment option for various IEIs is accumulating. Gene editing techniques for gene correction are, on the other hand, not in clinical use yet, despite rapid developments during the past decade. Current studies are focussing on improving rates of targeted integration, while preserving the primitive HSC population, which is essential for future clinical translation.

Summary
As HSC GT is becoming available for more diseases, novel developments should focus on improving availability while reducing costs of the treatment. Continued follow up of treated patients is essential for providing information about long-term safety and efficacy. Editing techniques have great potential but need to be improved further before the translation to clinical studies can happen.
Exhaled nitric oxide in asthma: from diagnosis to management
Authors: Guida Giuseppe , Carriero Vitina , Bertolini Francesca , Pizzimenti Stefano , Heffler Enrico , Paoletti Giovanni , Ricciardolo Fabio L.M. 
Published: December 2022

Purpose of review
Exhaled nitric oxide (FENO) is a noninvasive marker of eosinophilic airway inflammation, therefore, highly informative in asthma. Although FENO measurement is a potentially accessible tool to many physicians, recommendations regarding its clinical utility in diagnosing or tailoring treatment have not reached the expected diffusion. More recently FENO emerged as a biomarker for type-2 asthma phenotyping and a predictor of response to biologics.

Recent findings
The physiological discoveries and relevant acquisitions in clinical practice regarding FENO in asthma are presented. The FENO story draw a wavy path, characterized by promising findings, exciting confirmations and periods of low visibility. FENO emerged as a tool to increase the probability of asthma diagnosis. FENO predicts response to inhaled glucocorticoids (ICS), favoring the development of tailored treatment strategies and unrevealing nonadherence to ICS in difficult-to-treat or uncontrolled asthma. Finally, FENO was associated with a more severe phenotype and became a consolidated biomarker of type-2 inflammation.

Summary
FENO demonstrated to be a noninvasive and very reproducible test, encompassing many applications in the field of asthma management. Its routinely use, according to international guidelines, may improve the quality of patient assistance, from difficult-to-treat cases to biologic monitoring.
Identification of Subtypes of Dry Eye Disease, Including a Candidate Corneal Neuropathic Pain Subtype Through the Use of a Latent Class Analysis
Authors: Liu Zijun , Lietman Tom , Gonzales John A. 
Published: December 2022

Purpose:
In the absence of a gold-standard diagnostic test for different subtypes of dry eye disease (DED), we aimed to identify latent subtypes of DED within a well-characterized cohort.

Design:
This is a cross-sectional study of participants enrolled in the Sjögren International Collaborative Clinical Alliance (SICCA).

Methods:
A latent class analysis was applied to different dry eye–related signs/tests and symptoms of ocular pain (particularly those that aligned with corneal neuropathic pain) giving relative specificities and sensitivities of each diagnostic test or symptom in the SICCA population.

Results:
Four subtypes of DED were identified with putative designations including normal, asymptomatic dry eye, symptomatic dry eye, and corneal neuropathic pain.

Conclusions:
More specific classification criteria are needed for DED. Latent class analysis applied to the signs and symptoms captured in the SICCA cohort may allow for the development and refinement of classification criteria for specific subtypes of dry eye.
Home oxygen monitoring and therapy: learning from the pandemic
Authors: Beaney Thomas , Clarke Jonathan 
Published: December 2022

Purpose of review
Home oxygen monitoring and therapy have been increasingly used in the management of patients with chronic diseases. The COVID-19 pandemic has prompted the rapid uptake of remote monitoring programmes to support people with COVID-19 at home. This review discusses the recent evidence and learning in home oxygen monitoring and therapy from the pandemic.

Recent findings
Many home oxygen monitoring programmes were established around the world during the pandemic, mostly in high-income countries to support early detection of hypoxaemia and/or early hospital discharge. The characteristics of these programmes vary widely in the type of monitoring (self-monitoring or clinician-monitoring) and the patient risk groups targeted. There is a lack of evidence for benefits on clinical outcomes, including mortality, and on reductions in healthcare utilisation or cost-effectiveness, but programmes are viewed positively by patients. Recent studies have highlighted the potential bias in pulse oximetry in people with darker skin.

Summary
Recent evidence indicates that home oxygen monitoring therapy programmes are feasible in acute disease, but further research is needed to establish whether they improve patient outcomes, are cost-effective and to understand their equity impact.
The organization of double-stranded RNA in the chikungunya virus replication organelle
Authors: Laurent Timothée , Carlson Lars-Anders 
Published: December 2022

AbstractAlphaviruses are mosquito-borne, positive-sense single-stranded RNA viruses. Amongst the alphaviruses, chikungunya virus is notable as a large source of human illness, especially in tropical and subtropical regions. When they invade a cell, alphaviruses generate dedicated organelles for viral genome replication, so-called spherules. Spherules form as outward-facing buds at the plasma membrane, and it has recently been shown that the thin membrane neck that connects this membrane bud with the cytoplasm is guarded by a two-megadalton protein complex that contains all the enzymatic functions necessary for RNA replication. The lumen of the spherules contains a single copy of the negative-strand template RNA, present in a duplex with newly synthesized positive-sense RNA. Less is known about the organization of this double-stranded RNA as compared to the protein components of the spherule. Here, we analyzed cryo-electron tomograms of chikungunya virus spherules in terms of the organization of the double-stranded RNA replication intermediate. We find that the double-stranded RNA has a shortened apparent persistence length as compared to unconstrained double-stranded RNA. Around half of the genome is present in either of five conformations identified by subtomogram classification, each representing a relatively straight segment of ~25-32 nm. Finally, the RNA occupies the spherule lumen at a homogeneous density, but has a preferred orientation to be perpendicular to a vector pointing from the membrane neck towards the spherule center. Taken together, this analysis lays another piece of the puzzle of the highly coordinated alphavirus genome replication.
ATM-Mediated Translocation of RanBPM Regulates DNA Damage Response by Stabilizing p21 in Non-Small Cell Lung Cancer Cells
Authors: Deng Tanggang , Xie Lin , Xiao Yugang , Zhang Zhenbin , Peng Yuchong , Yin Linglong , Fu Yongming , Li Xiong 
Published: December 2022

AbstractNon-small cell lung cancer (NSCLC) is the leading cause of cancer-induced deaths around the world, and platinum-based chemotherapy remains a standard-of-care for most patients with advanced NSCLC. DNA damage response (DDR) induced by platinum or Etoposide activated a panel of cell cycle-regulatory proteins including p21 through p53 pathway. In this present study, we found that the level of p21 or RanBPM is lower in NSCLC than non-malignant tissues and has a highly positive correlation, which is negatively correlated with the survival of patients. We further revealed that RanBPM protein physically interacts with p21, RanBPM deubiquitinates p21 by recruiting a deubiquitinase USP11 to maintain protein stability of p21. Furthermore, RanBPM regulates DNA damage response (DDR) in a p21-dependent manner, and DNA damage promotes the translocation of RanBPM into the nucleus and regulates p21 protein stability through ATM-mediated pathways. We for the first time revealed a novel mechanism of p21 protein stability regulated by RanBPM, and the novel roles of RanBPM in the regulation of DDR.
pOpsicle: An all-optical reporter system for synaptic vesicle recycling combining pH-sensitive fluorescent proteins with optogenetic manipulation of neuronal activity
Authors: Seidenthal Marius , Jánosi Barbara , Rosenkranz Nils , Schuh Noah , Elvers Nora , Willoughby Miles , Zhao Xinda , Gottschalk Alexander 
Published: December 2022

AbstractpH-sensitive fluorescent proteins are widely used to study synaptic vesicle (SV) fusion and recycling. When targeted to the lumen of SVs, fluorescence of these proteins is quenched by the acidic pH. Following SV fusion, they are exposed to extracellular neutral pH, resulting in a fluorescence increase. SV fusion, recycling and acidification can thus be tracked by tagging integral SV proteins with pH-sensitive proteins. Neurotransmission is generally stimulated by electrophysiology, which is not feasible in small, intact animals, thus limiting the approach to cell culture regimes. Previousin vivoapproaches depended on distinct (sensory) stimuli, thus limiting the addressable neuron types. To overcome these limitations, we established an all-optical approach to stimulate and visualize SV fusion and recycling. We combined distinct pH-sensitive fluorescent proteins (inserted into the SV protein synaptogyrin) and light-gated channelrhodopsins (ChRs) for optical stimulation, overcoming optical crosstalk and thus enabling an all-optical approach. We generated two different variants of thepH-sensitiveoptogenetic reporter of vesiclerecycling (pOpsicle) and tested them in cholinergic neurons of intactCaenorhabditis elegansnematodes. First, we combined the red fluorescent protein pHuji with the blue-light gated ChR2(H134R), and second, the green fluorescent pHluorin combined with the novel red-shifted ChR ChrimsonSA. In both cases, fluorescence increases were observed after optical stimulation. Increase and subsequent decline of fluorescence was affected by mutations of proteins involved in SV fusion and endocytosis. These results establish pOpsicle as a non-invasive, all-optical approach to investigate different steps of the SV cycle.
In vivo measurement of the Young’s modulus of the cell wall of single root hairs
Authors: Pereira David , Alline Thomas , Asnacios Atef 
Published: December 2022

AbstractRoot hairs are cells from the root epidermis that grow as long tubular bulges perpendicular to the root. They can grow in a variety of mechanical or chemical environments. Their mechanical properties are mainly due to their stiff cell wall which also constitutes a physical barrier between the cell and its environment. Thus, it is essential to be able to quantify the cell wall mechanical properties and their adaptation to environmental cues. Here, we present a technique we developed to measure the Young’s (elastic) modulus of the root hair cell wall. In essence, using custom-made glass microplates as cantilevers of calibrated stiffness, we are able to measure the force necessary to bend a single living root hair. From these experiments one can determine the stiffness and Young’s modulus of the root hair cell wall.
Tricarboxylic acid (TCA) cycle, sphingolipid, and phosphatidylcholine metabolism are dysregulated inT. gondiiinfection-induced cachexia
Authors: Feng Tzu-Yu , Melchor Stephanie J. , Ghumman Haider , Kester Mark , Fox Todd E. , Ewald Sarah E. 
Published: December 2022

SummaryCachexia is a life-threatening disease characterized by chronic, inflammatory muscle wasting and systemic metabolic impairment. Despite its high prevalence, there are no efficacious therapies for cachexia. Mice chronically infected with the protozoan parasiteToxoplasma gondiirepresent a novel animal model recapitulating the chronic kinetics of cachexia. To understand how perturbations to metabolic tissue homeostasis influence circulating metabolite availability we used mass spectrometry analysis. Despite the significant reduction in circulating triacylglycerides, non-esterified fatty acids, and glycerol, sphingolipid long-chain bases and a subset of phosphatidylcholines (PCs) were significantly increased in the sera of mice withT. gondiiinfection-induced cachexia. In addition, the TCA cycle intermediates α-ketoglutarate, 2-hydroxyglutarate, succinate, fumarate, and malate were highly depleted in cachectic mouse sera. Sphingolipids and their de novo synthesis precursors PCs are the major components of the mitochondrial membrane and regulate mitochondrial function consistent with a causal relationship in the energy imbalance drivingT. gondii-induced chronic cachexia.
Is intuition better than rationality? The effect of pre-decisional strategy on occupational interest forecasting in Chinese college students
Authors: Lu Di , Jiao Run Kai , Li Fei-Fei , Yin Hang , Lin Xiaoqing 
Published: December 2022

PurposePrevious studies showed that the unconscious-intuitive strategy resulted in a better choice for it is more predictive of actual interest. This benefit may be influenced by occupational engagement, for the dual process of career decisions takes it as a tool for multidevelopment and optimal adjustment. Thus, we replicated (and extended) the study of Motl et al. (2018) through two experiments to identify the role of three pre-decisional strategies and then explore the combined effects of occupational engagement and these strategies. The purpose of this paper is to address these issues.Design/methodology/approachThe authors replicated (and extended) the study of Motl et al. (2018) through two experiments. First, both studies adopted generalized linear mixed-effects models for statistical analyses to distinguish random and fixed effects. Second, Study 2 used a computer-based process-tracing program called “Mouselab” to explore the effect of the pre-decisional strategy self-generated on participants' interest appraisals over time.FindingsStudy 1 found that engagement helped promote participants' interest experience when decisions as usual and the intuitive strategy did not produce optimal choices. Further, people with more prior knowledge about situations no longer achieved as many benefits from their allocated strategy (i.e. rational strategy) as those with less. Study 2 failed to find adequate advantages of the intuitive strategy. Specifically, people with less search depth (the heuristic-intuitive strategy) were more interested in their choices. Nevertheless, when the strategy was manipulated as variability of search (VS), it only found the promotion of engagement, but it neither found the interaction between engagement and strategy nor did strategy itself.Originality/valueThe present paper provides mixed support for adaptive career decision-making. Career counselors can use occupational engagement levels as a reference for pre-decisional strategy selection and coach clients to adopt a proper decision-making process/method to make interest forecasts.
Application of fluorescence in situ hybridization in distinguishing acral melanoma in situ from acral junctional melanocytic nevus on the volar skin in Japanese patients
Authors: Takai Sayaka , Arai Eiichi , Shojiguchi Naoko , Nakamura Yasuhiro , Momose Shuji , Fukuda Tomoo , Ishizawa Keisuke , Ogata Dai , Tsunemi Yuichiro , Nakamura Koichiro , Tsuchida Tetsuya 
Published: December 2022

AbstractFour‐colored fluorescence in situ hybridization (FISH) is an ancillary diagnostic tool for melanoma. However, most studies that have investigated the usefulness of FISH primarily focused on advanced melanomas. The aim of the current study was to evaluate the effectiveness of FISH in distinguishing acral melanoma (AM) in situ from benign acral junctional nevus (AJN), two types of lesions that are difficult to differentiate via traditional clinical means. The authors investigated the usefulness of FISH in 91 acral melanocytic lesions, including 50 lesions with diagnostic discrepancies between dermoscopic and pathologic approaches or difficulty diagnosing between AM in situ and AJN, on the volar skin of Japanese patients. The authors classified the lesions based on the diagnosis of dermatologists and pathologists into four groups: (I) lesions with a unanimous diagnosis by dermatologists and pathologists as AM in situ or AJN (n = 41); (II) lesions with a unanimous diagnosis by dermatologists only as AM in situ or AJN (n = 21); (III) lesions with a unanimous diagnosis by pathologists only as AM in situ or AJN (n = 15); and (IV) all other lesions (n = 14). The dermatologists diagnosed the lesions by clinical and dermoscopic photographs alone, while the pathologists diagnosed the lesions by microscopy of hematoxylin and eosin–stained slides alone. In group I (AM in situ [n = 20] and AJN [n = 21]), four‐colored FISH demonstrated 90% sensitivity and 81% specificity in distinguishing AM in situ from AJN. There was a significant correlation between the FISH results and the unanimous diagnoses by pathologists alone (p = 0.03) in group III. However, FISH results were not significantly correlated with the unanimous diagnoses by dermatologists alone (p = 0.33) in group II. In conclusion, the four‐colored FISH probe kit was useful in distinguishing between AM in situ and AJN and may be an ancillary method when pathologists who are not experts of dermatopathology diagnose melanocytic lesions.