bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromium-Promoted Dearomative (Deutero)Hydrocyanoalkylation of (Hetero)Arenes Using Simple Alkylnitriles
Authors: Li Wei , Zeng Wei-Long , Jiang Xu
Published: October 2023

Herein, a general strategy for the regioselective dearomative 1,2-hydrocyanoalkylation of chromium-bound (hetero)arenes with simple alkylnitriles as pronucleophiles was disclosed, providing rapid access to 1,3-cyclohexadienes possessing useful alkylnitrile groups. The versatility of this methodology further enabled a selective dearomative deuteration reaction. Finally, synthetic applications of the method in the formal synthesis of natural products, including erysotramidine, demethoxyerythratidinone, and morphine, were demonstrated.
Synthesis of 2,4-Disubstituted Oxazoles by a Copper-Catalyzed [3+2] Annulation/Olefination Cascade between Amides and IIII/PV Hybrid Ylides
Authors: Wang Zhaofeng , Ye Xingchen
Published: October 2023

We report a novel and efficient method for oxazole synthesis through a copper-catalyzed [3+2] annulation/olefination cascade between readily available iodonium–phosphonium hybrid ylides and amides. An unprecedented α-phosphonium Cu carbenoid acts as the key intermediate. This method features excellent regioselectivity with mild reaction conditions and a broad substrate scope. Its synthetic utility is demonstrated by its application in late-stage functionalizations and the rapid synthesis of a chiral ligand based on an oxazole motif.
Mapping crisis communication in the communication research: what we know and what we don’t know
Authors: Upadhyay Shalini , Upadhyay Nitin
Published: October 2023

This paper presents a comprehensive analysis of crisis communication research from 1968 to 2022, utilizing bibliometric methods to illuminate its trajectories, thematic shifts, and future possibilities. Additionally, it presents foundational themes such as crisis communication and social media, health communication, crisis and leadership, and reputation and advertising. This analysis offers not only historical insights but also serves as a roadmap for future research endeavors. Furthermore, this study critically evaluates over five decades of scholarship by unveiling the intellectual, social, and conceptual contours of the field while highlighting thematic evolutions. Employing diverse bibliometric indices, this research quantifies authors’ and nations’ productivity and impact. Through co-word analysis, four thematic clusters emerge, capturing the dynamic nature of crisis communication research. However, the study also reveals limited collaboration among authors, primarily localized, indicating room for enhanced cross-border cooperation and exploration of emerging themes. The study’s social network analysis sheds light on key actors and entities within the crisis communication realm, underscoring opportunities to fortify global networks for a robust crisis communication spectrum. Beyond academic curiosity, these insights hold practical implications for policymakers, scholars, and practitioners, offering a blueprint to enhance crisis communication’s effectiveness. This study’s findings can be considered as a reference point for future studies in crisis communication.
Exponential decay estimates for the damped defocusing Schrödinger equation in exterior domains
Authors: Cavalcanti Marcelo M. , Corrêa Wellington J. , Domingos Cavalcanti Valéria Neves
Published: October 2023

We are concerned with the existence as well as the exponential stability in H1-level for the damped defocusing Schrödinger equation posed in a two-dimensional exterior domain Ω with smooth boundary ∂Ω. The proofs of the existence are based on the properties of pseudo-differential operators introduced in Dehman et al. [Math. Z. 254, 729–749 (2006)] and a Strichartz estimate proved by Anton [Bull. Soc. Math. Fr. 136, 27–65 (2008)], while the exponential stability is achieved by combining arguments firstly considered by Zuazua [J. Math. Pures Appl. 9, 513–529 (1991)] for the wave equation adapted to the present context and a global uniqueness theorem. In addition, we proved propagation results for the linear Schrödinger equation for any dimensional and for any (reasonable) boundary conditions employing microlocal analysis.
Highly improved light harvesting and charge separation of TiO2/N719 photoanodes using surface NiTiO3 quantum dot decoration
Authors: Chen Dong , Sun Guo Wen , Pan Jiang Long , Wang Sha Sha , Yang Xi Yin , Wang Yan Chun , Gao Xiu Ping , Sun Geng Zhi , Pan Xiao Jun , Zhou Jin Yuan
Published: October 2023

Conventional TiO2/N719 photoanodes often suffer from the limited visible light absorption (450–500 nm) and the serous recombination of photo-generated carries (e−/h+)/electrolyte ions (I3−), accordingly outputting a low photoelectronic conversion efficiency (PCE). In this work, a type of strawberry-like TiO2/NiTiO3 (NTO) nanospheres was designed via a simple hydrothermal method. In this design, the NTO quantum dots (QDs) with size of several nanometers were decorated on the surface of TiO2 nanospheres. This TiO2/NTO nanostructure can not only enhance the visible light absorption of the TiO2/N179 photoanodes but also improve the separation of photo-generated carriers and depress the recombination of e−/h+ and I3−. Thus, the optimal TiO2/NTO/N719 dye-sensitized solar cells (DSSCs) achieved greatly improved Jsc and Voc, both of which result into a 32.8%-improved PCE compared to the TiO2/N719 ones. These improvements could be due to the decreased charge transfer resistance at the photoanode/electrolyte interface (Rct2) and the increased electron lifetime (τn) caused by TiO2/NTO hetero-interface. In addition, the optimization on NTO QDs indicates that the density of QDs main affects the τn, and the size of QDs affects with Rct2. Moderate density and size (ca. 5 nm) of QDs can optimize the photoelectronic performances of DSSCs.
Ga doping induced thermal stabilization of fcc phase in Ge2Sb2Te5 thin films: A step toward power-efficient phase change memories
Authors: Bala Neeru ,   Manju, Goutam U. K. , Thakur Anup
Published: October 2023

Ge2Sb2Te5 (GST), a phase change material, generally exhibits two-step crystallization (amorphous→fcc→hcp) to store and process data. The present study reports the crystallization behavior and bonding mechanism of Ga-doped GST thin films with thermal annealing. Ga doping results in the formation of Ga–Te bonds and shows no bonding with other host elements (Ge and Sb), which changes the bonding mechanism and leads to one-step crystallization (amorphous→fcc). The optical transmission contrast confirmed the thermal stabilization of the fcc phase with thermal annealing. These findings suggest that Ga doping into GST thin films has thermally stabilized the metastable fcc phase and suppressed the hcp phase, hence posing it as a potential candidate for phase change memory applications with fast processing speed and low power consumption.
Effect of pressure variations on film boiling characteristics of liquid nitrogen
Authors: Kumar Indradev , Roy Anindya Kanti , Hens Abhiram
Published: October 2023

Liquid nitrogen is a widely used cryogenic fluid in various industrial and scientific applications. Film boiling is inevitable when a hot surface is exposed to a cryogenic fluid like liquid nitrogen. This mode of boiling can affect the heat transfer rate and cooling efficiency of the process. The present study investigated the effect of operating pressure on film boiling characteristics of liquid nitrogen using continuum-based numerical simulations. Simulations were performed at atmospheric, intermediate, and near-critical pressures using a coupled level-set and volume of fluid method of interface tracking. Bubble dynamics and heat flux variations were examined at different degrees of wall superheat. The results show that the pressure condition significantly affects the bubble dynamics and boiling of liquid nitrogen. At higher pressure, the specific heat of the vapor phase increases, resulting in a higher heat transfer rate. It was also noted that at high levels of superheat, the bubbles detach from the heating surface faster, resulting in a higher transfer of heat. The effect of pressure on the number of bubble formation sites was also investigated. The simulations also reveal that the local thermodynamic conditions, such as pressure, temperature, and vapor concentration, significantly influence the bubble size.
Intrinsic structural dynamics dictate enzymatic activity and inhibition
Authors: Shukla Vaibhav Kumar , Siemons Lucas , Hansen D. Flemming
Published: October 2023

Enzymes are known to sample various conformations, many of which are critical for their biological function. However, structural characterizations of enzymes predominantly focus on the most populated conformation. As a result, single-point mutations often produce structures that are similar or essentially identical to those of the wild-type enzyme despite large changes in enzymatic activity. Here, we show for mutants of a histone deacetylase enzyme (HDAC8) that reduced enzymatic activities, reduced inhibitor affinities, and reduced residence times are all captured by the rate constants between intrinsically sampled conformations that, in turn, can be obtained independently by solution NMR spectroscopy. Thus, for the HDAC8 enzyme, the dynamic sampling of conformations dictates both enzymatic activity and inhibitor potency. Our analysis also dissects the functional role of the conformations sampled, where specific conformations distinct from those in available structures are responsible for substrate and inhibitor binding, catalysis, and product dissociation. Precise structures alone often do not adequately explain the effect of missense mutations on enzymatic activity and drug potency. Our findings not only assign functional roles to several conformational states of HDAC8 but they also underscore the paramount role of dynamics, which will have general implications for characterizing missense mutations and designing inhibitors.
On similative demonstratives in Czech and English
Authors: Janebová Markéta , Martinková Michaela
Published: October 2023

This paper is a contrastive corpus-based study of similative demonstratives, a major means of expressing
similarity and ad-hoc categorization. It explores the divergence between the Czech demonstrative takový and its
English dictionary equivalent such in their “atypical” – extended, or non-phoric – uses. Through the
triangulation of comparable fiction texts, their translation (from a bidirectional translation corpus) and spoken language data
(from comparable monolingual corpora of spoken English and Czech), converging evidence is found of the development of discourse
functions of the Czech takový which shows an increase in its intersubjectivity, not attested with
such, but common with the English type nouns sort, kind, and type. These
cross-linguistic parallels are not only relevant for current discussions on intersubjectivity and intersubjectification, but they
also call for further research on general patterns of ad-hoc categorization.
Predicting executive functioning from brain networks: modality specificity and age effects
Authors: Heckner Marisa K , Cieslik Edna C , Paas Oliveros Lya K , Eickhoff Simon B , Patil Kaustubh R , Langner Robert
Published: October 2023

Healthy aging is associated with structural and functional network changes in the brain, which have been linked to deterioration in executive functioning (EF), while their neural implementation at the individual level remains unclear. As the biomarker potential of individual resting-state functional connectivity (RSFC) patterns has been questioned, we investigated to what degree individual EF abilities can be predicted from the gray-matter volume (GMV), regional homogeneity, fractional amplitude of low-frequency fluctuations (fALFF), and RSFC within EF-related, perceptuo-motor, and whole-brain networks in young and old adults. We examined whether the differences in out-of-sample prediction accuracy were modality-specific and depended on age or task-demand levels. Both uni- and multivariate analysis frameworks revealed overall low prediction accuracies and moderate-to-weak brain–behavior associations (R2 < 0.07, r < 0.28), further challenging the idea of finding meaningful markers for individual EF performance with the metrics used. Regional GMV, well linked to overall atrophy, carried the strongest information about individual EF differences in older adults, whereas fALFF, measuring functional variability, did so for younger adults. Our study calls for future research analyzing more global properties of the brain, different task-states and applying adaptive behavioral testing to result in sensitive predictors for young and older adults, respectively.
Coordinating farms in collective agri-environmental schemes: the role of conditional incentives
Authors: Limbach Kristin , Rozan Anne
Published: September 2023

This paper analyses data from a novel collective agri-environmental scheme (cAES) in Alsace, France, designed to protect the local European hamster population by motivating farmers to engage in habitat conservation measures. In contrast to typical conservation contracts that pay individual farmers based on their own performance, the cAES studied here pays farmers only when the percentage of land conserved by all farmers within a collective zone reaches a critical threshold. We find that the likelihood of participation is higher for farmers with a relatively large agricultural surface within the collective zone, increases with the number of farmers in a collective zone, and increases over time. Those with more land in the collective zone allocate more acreage to conservation. We define different contributor types and provide insight into the possible motives underlying contributions to collective conservation schemes.
Demand for Statehood: The Case of Native Military Recruitment in World War II
Authors: Yi Joowon
Published: September 2023

This paper examines how the demand for independence appeared in the era of Decolonization. I argue that nationalist movements were more likely to emerge in places where the colonial authorities recruited the native population in World War II. The theory highlights the role of war veterans in creating the demand for independence and in facilitating it through organized collective action. Drawing on original World War II native recruitment data, an analysis of nationalist movements in sub-national units from 1945 to 1984 provides evidence consistent with the theory. The findings in this study help us better understand the rise of nationalist movements in the twentieth century and the political effects of military service.
The Power of Personal Archives in Witnessing, Teaching, and Visual Storytelling: The Armenian Memory Project
Authors: Masud Catherine , Marsoobian Armen T
Published: September 2023

The Armenian Memory Project (AMP) is a collaborative effort designed to harness the energy and resources of the University of Connecticut and the New England Armenian community for the goal of fostering greater understanding of the region’s Armenian cultural heritage and the impact human rights crimes had on the Armenian community. In 2019, students and faculty from the university worked with Armenian American institutions and individuals on an initial component of the AMP, employing digital media technology to tell the story of one immigrant Armenian family, the Dildilians. A unique course was created to produce a documentary film centring around this family’s experiences in Ottoman Turkey before, during, and after the Armenian Genocide. Designed and taught by a documentary filmmaker with support from a family archivist/historian, the course brought students together in a collaborative learning experience. By immersing themselves in the family’s extensive photograph archive, these students came to understand the important role that the past continues to play in the lives of present-day Armenians. Furthermore, by taking on the responsibility as storytellers of the Dildilian narrative, students developed a deeper identification with this distant history and, in a wider sense, an appreciation for the ethical value of memory in bearing witness to the past. This collaborative and participatory framework for teaching using archival collections can serve as a model for creating a transformative learning experience in the study of human rights, war, and genocide.
Relativistic binary-disc dynamics and the timing of OJ-287’s flares
Authors: Zwick Lorenz , Mayer Lucio
Published: October 2023

We revisit the precessing black hole binary model, a candidate to explain the bizarre quasi-periodic optical flares in OJ-287’s light curve, from first principles. We deviate from existing work in three significant ways: (1) Including crucial aspects of relativistic dynamics related to the accretion disc’s gravitational moments. (2) Adopting a model-agnostic prescription for the disc’s density and scale height. (3) Using Markov chain Monte Carlo methods to recover reliable system parameters and uncertainties. We showcase our model’s predictive power by timing the 2019 Eddington flare within 40 h of the observed epoch, exclusively using data available prior to it. Additionally, we obtain a novel direct measurement of OJ-287’s disc mass and quadrupole moment exclusively from the optical flare timings. Our improved methodology can uncover previously unstated correlations in the parameter posteriors and patterns in the flare timing uncertainties. According to the model, the 26th optical flare is expected to occur on the 21st of August 2023 ± 32 d, shifted by approximately a year with respect to previous expectations.
Consenting Under Coercion: The Partial Validity Account
Authors: Bajaj Sameer , Tomlin Patrick
Published: September 2023

How is the validity of our consent, and others’ moral permission to act on our consent affected by coercion? Everyone agrees that in cases of two-party coercion—when X coerces Y to do something with or for X—the consent of the coerced is invalid, and the coercer is not permitted to act upon the consent they receive. But coercers and the recipients of consent are not always identical. Sometimes a victim, Y, agrees to do something to, with, or for Z because they are being coerced by X. Recently, several philosophers have argued that consent under third-party coercion can be fully valid. We argue that this view has troubling implications. We develop a novel view of consent in third-party coercion cases, which we call the partial validity account. The core idea is that, under severe coercion, Y’s consent is at most partially valid—it reduces the strength of, but does not completely dissolve, Z’s consent-sensitive duties. We argue that the partial validity account gets the right results in important cases and explains the moral factors at play better than alternative accounts.
Identification of microRNAs involved in ectomycorrhizal formation in Populus tomentosa
Authors: Tao Yuanxun , Li Chaofeng , Liu Ying , Xu Changzheng , Okabe Shin , Matsushita Norihisa , Lian Chunlan
Published: September 2023

The majority of woody plants are able to form ectomycorrhizal (ECM) symbioses with fungi. During symbiotic development, plants undergo a complex re-programming process involving a series of physiological and morphological changes. MicroRNAs (miRNAs) are important components of the regulatory network underlying symbiotic development. To elucidate the mechanisms of miRNAs and miRNA-mediated mRNA cleavage during symbiotic development, we conducted high-throughput sequencing of small RNAs and degradome tags from roots of Populus tomentosa inoculated with Cenococcum geophilum. This process led to the annotation of 51 differentially expressed miRNAs between non-mycorrhizal and mycorrhizal roots of P. tomentosa, including 13 novel miRNAs. Increased or decreased accumulation of several novel and conserved miRNAs in ECM roots, including miR162, miR164, miR319, miR396, miR397, miR398, novel-miR44 and novel-miR47, suggests essential roles for these miRNAs in ECM formation. The degradome analysis identified root transcripts as miRNA-mediated mRNA cleavage targets, which was confirmed using real-time quantitative PCR. Several of the identified miRNAs and corresponding targets are involved in arbuscular mycorrhizal symbioses. In summary, increased or decreased accumulation of specific miRNAs and miRNA-mediated cleavage of symbiosis-related genes indicate that miRNAs play important roles in the regulatory network underlying symbiotic development.
Perioperative Chemotherapy and Chemoradiotherapy for Patients With Resectable and Borderline Resectable Pancreatic Adenocarcinoma
Authors: Coveler Andrew L. , Pillarisetty Venu G. , Koh Wui-Jin , Zhen David B. , Park James O. , King Gentry G. , Sham Jonathan G. , Hannan Lindsay M. , Mann Gary N. , Baker Kelsey K. , Redman Mary W. , Swanson Paul E. , Chiorean E. Gabriela , Whiting Sam H.
Published: October 2023

Objectives

Pancreatic ductal adenocarcinoma (PDA) is the third most common cause of cancer death in the United States. Most patients who undergo resection develop recurrence. Standard treatment confers a median overall survival (OS) of 24 months. Exposure to alternate regimens may prevent chemoresistance. This study evaluated multiagent perioperative therapy for potentially resectable PDA patients to improve OS.

Methods

A single center, phase 2, trial of patients with resectable or borderline resectable PDA. Patients received neoadjuvant therapy with induction chemotherapy (gemcitabine, docetaxel, capecitabine) for 3 cycles, chemoradiation (intensity-modulated radiation therapy with capecitabine and oxaliplatin) followed by surgery, and 2 months of adjuvant gemcitabine and oxaliplatin and 2 months of gemcitabine. The primary endpoint was OS. The secondary endpoint was recurrence-free survival (RFS).

Results

Thirty-two eligible patients were enrolled. Twenty-two patients underwent surgical resection. After a median follow-up of 56.8 months, mOS was 31.6 months (95% confidence interval [CI], 14.2–58.1) for all patients, 58.1 months (95% CI, 31.6 to NR) for those who completed surgery. The mRFS was 31.3 months (95% CI, 12.5 to NR).

Conclusions

Perioperative therapy with GTX, chemoradiotherapy, and adjuvant GemOx/Gem resulted in promising survival of 58 months for patients who underwent resection and may represent another treatment option for PDA.
Prevalence of Parent Mental Health Problems in an Interdisciplinary Feeding Clinic: Short Communication
Authors: Bakula Dana M. , Wallisch Anna , Slosky Laura , Dean Kelsey , Davis Ann , Edwards Sarah
Published: October 2023

Parents of children with pediatric feeding disorder (PFD) often experience high stress and may be at advanced risk for mental health conditions. We conducted a retrospective chart review of 413 parents who completed intake surveys at an interdisciplinary feeding clinic to determine the prevalence and types of mental health conditions among parents; 41.8% of parents reported a mental health diagnosis among the mother and/or father. Of the parents with mental health conditions, the most prevalent conditions reported were anxiety (71.1% for mothers, 50% for fathers) and mood disorders (62.7% for mothers, 40.9% for fathers). For mothers, 21.1% indicated their mental health disorder had a postpartum onset. Parents of children with birth complications were more likely to have a mental health condition (50.9%) than parents of children without a birth complication (38.7%), and parents reporting mental health conditions had children with significantly more co-occurring medical conditions. Since parent stress and mental health can influence parent-child interactions during mealtime, this study suggests the importance of addressing both parent mental health factors and child factors when treating children for PFD. Future studies are needed to develop novel interventions that support the specific mental health needs of parents of children with PFD.
Relating Therapy for Distressing Voices in the Context of Anorexia Nervosa
Authors: Pugh Matthew , Bibby-Jones Anna-Marie , Coyle-Stewart Annabel , Hayward Mark
Published: October 2023

Voice hearing experiences are commonly reported by patients with anorexia nervosa (AN) and are associated with negative outcomes. The “eating disorder voice” (EDV) can be understood within relational frameworks. Relating therapy (RT) has offered encouraging outcomes when targeted at voice hearing experiences transdiagnostically but has not been evaluated in the context of AN. This study aimed to offer a preliminary and mixed methods exploration of RT for the EDV. RT was delivered to three participants with a diagnosis of AN who were distressed by an EDV. Weight, negative impact of voices, and eating disorder cognitions were assessed at baseline, posttherapy and at brief follow-up. Participant experiences were explored through exit interviews. Therapy was completed by all participants. Weight gain was reported by two participants and maintained at brief follow-up. Positive changes were not reported on other measures. Qualitative data were suggestive of positive experiences that facilitated assertive responding.
Impact of Mental Health Legislation on Public Interest and Awareness of Common Mental Disorders
Authors: Alibudbud Rowalt
Published: October 2023

This study explored online public interest using search volumes for various mental disorders using an infodemiological design. Google Trends search volumes for schizophrenia, bipolar disorder, major depressive disorder, anxiety disorder, and substance abuse from January 2004 to December 2021 in the Philippines were described and compared. In addition, interrupted time series and mean comparisons were done to determine the impact of the Philippine Mental Health Act. Findings show that public interest was highest for major depressive disorder, followed by anxiety disorder, substance abuse, bipolar disorder, and schizophrenia. Among them, public interest in schizophrenia, major depressive disorder, bipolar disorder, and substance abuse improved following the Act's legislation. The uneven stigma of mental disorders and the incomplete implementation and unequal focus of Philippine mental health promotion programs can explain these findings. Thus, mental disorders with low public interest should be given attention in mental health awareness activities.
The social equity and the spatial accessibility of general hospitals in big Chinese cities: an exploration based on different income groups and transportation modes in Shenzhen
Authors: Xia Yuanxiang , Zhu Wenjian
Published: October 2023

Objectives:

The rational planning and allocation of hospitals significantly improve residents’ health and quality of life. However, the unequal allocation of medical resources remains a significant issue in large Chinese cities. This study investigated the disparities in access to health care among different social groups in Shenzhen and explored the discrepancy in equity and its influencing mechanisms.

Methods:

The population was divided into 5 social groups based on housing prices: high-income, middle-high income, middle-income, middle-low income, and low-income. The actual travel times of residential neighborhoods and general hospitals under both driving and public transportation were accessed through the application programming interface Amap, a mapping technology application. The accessibility of general hospitals was calculated by the Gaussian-based 2-step floating catchment area method. The Gini coefficient was used to further investigate the equity in medical facility services.

Results:

Accessibility to first and second-level hospitals was adequate for the high-income group. However, a significant spatial mismatch in the allocation of hospitals was identified for the middle-low income and low-income groups, especially those reliant on public transportation.

Conclusions:

This study reveals an inequitable allocation of hospitals, with driving accessibility generally superior to public transport accessibility in Shenzhen, and a significant spatial mismatch for middle-low income and low-income groups. This study suggests optimizing public transportation around hospitals and middle-low income or low-income neighborhoods through urban planning to improve the accessibility of public service facilities for middle-low income and low-income households, thereby promoting more health equity.
Can Whole-Body Magnetic Resonance Imaging Predict Relapse in Juvenile Idiopathic Arthritis? A Longitudinal Pilot Study
Authors: Bhalla Deeksha , Bagri Narendra , Jana Manisha , Upadhyay Ashish Datt
Published: October 2023

Objective

To determine the utility of whole-body magnetic resonance imaging (WB MRI) to predict relapse in children with juvenile idiopathic arthritis (JIA) in clinical remission.

Methods

Consecutive patients with JIA who fulfilled the Wallace criteria for remission were recruited into this longitudinal pilot study and underwent WB MRI. A radiological score was devised, incorporating synovitis, bone marrow edema, sacroiliitis, enthesitis, and bone erosions. Two readers independently scored the MR data sets. The same score was calculated for both knee joints individually and correlated with outcome for that joint. Score-based models incorporating clinical and laboratory variables were generated. Logistic regression analysis was done to determine predictors for relapse. Receiver operating characteristic curve was drawn for significant variables.

Results

Twenty-two children (median age, 12 years; interquartile range, 9.5–14.25 years) were included in the final analysis. At 24 months' follow-up, 15 joints in 5 children relapsed; knee was the most common site. Seven knee joints had disease relapse. On univariate analysis, synovitis and total score on WB MRI were significant predictors of relapse at follow-up, with odds ratios of 9.46 (bias-corrected 95% confidence interval, 3.07–29.13) and 2.8 (bias-corrected 95% confidence interval, 1.23–6.39) respectively. Two models, which included a higher number of joints involved at presentation and abrupt drug withdrawal strategy as predictor variables, were also statistically significant (odds ratio, approximately 1.9). On multivariate analysis of the predictors variables in models where p < 0.6, it was found that only synovitis score and total score were near statistical significance (p = 0.06); no clinical or laboratory variables were significant. The areas under the receiver operating characteristic curve for relapse prediction were approximately 0.82, 0.87, 0.79, and 0.81 for synovitis score, total MRI score, and both models, respectively.

Conclusion

Synovitis on WB MRI is the strongest independent predictor for disease relapse in children with JIA in remission
Eating disorders in transgender and gender diverse people: characteristics, assessment, and management
Authors: Keski-Rahkonen Anna
Published: October 2023

Purpose of review

This review summarizes recent research on eating disorders among gender minorities, transgender and gender diverse people. The focus is on research published in 2022 and the first half of 2023.

Recent findings

Up to 1.2% of young people and 0.3–0.5% of adults identify as transgender, and 2.7–8.4% of young people and 0.3–4.5% of adults report some degree of gender diversity. About 20–50% of transgender and gender diverse people report engaging in disordered eating and >30% screen positive for eating disorder symptoms, and 2–12% have received an eating disorder diagnosis from a health professional. Many transgender and gender diverse people describe eating disorder symptoms as a way of coping with gender dysphoria. They also report high levels of mental and behavioral symptoms, particularly mood and anxiety disorders, suicidal thoughts and behaviors, trauma-related symptoms and disorders, alcohol and substance use, and autism. Gender minorities frequently experience discrimination, victimization, and violence, primarily sexual and physical violence. The minority stress model attributes mental health symptoms to these factors. Promising interventions based on the minority stress model have recently become available, but more research is needed on how to support transgender and gender diverse people with eating disorders. To manage eating disorders in this population, gender-affirming care should be combined with specialist eating disorder treatment.

Gender minorities are at high risk for eating disorders. Future studies should assess what is the most appropriate treatment for transgender and gender diverse people with eating disorders.
Effect of Baduanjin exercise of obstructive sleep apnea-hypopnea in chronic obstructive pulmonary disease: a study protocol for a randomized, single-blind, controlled trial
Authors: Zhang Xi , Cai Yi-hang , Ye Kang-Jie , Li Yu-Jin , Li Ji-Qiang , Zhang Zhong-De
Published: September 2023

Background

Baduanjin is one of the traditional Chinese treatments for respiratory diseases. However, its effects on overlap syndrome (obstructive sleep apnea-hypopnea and chronic obstructive pulmonary disease) have not been rigorously tested. This study aims to evaluate the benefits and safety of Baduanjin treatment in chronic obstructive pulmonary disease (COPD) patients with obstructive sleep apnea-hypopnea (OSAH).

Methods

COPD patients with OSAH will be randomly allocated in a 1:1 ratio to Baduanjin group or control group. Both groups receive continuous positive airway pressure therapy and basic medication for 12 weeks. Baduanjin group will receive additional instructional Baduanjin exercises. The primary outcomes are BODE index. The secondary outcomes are polysomnogram, cardiopulmonary exercise test, Beck Depression Scale-II, and Saint George’s Respiratory Questionnaire.

Discussion

This trial will provide preliminary evidence about the efficacy and safety of Baduanjin exercise for COPD patients with OSAH. Baduanjin exercises may become an additional option for pulmonary rehabilitation of OSA-COPD overlap syndrome.

Trial registration

ClinicalTrials.gov, ID: NCT ChiCTR2200063171. Registered retrospectively on 1 June 2022.
The Physical Biology of Nucleolus Disassembly
Authors: Pham An T. , Mani Madhav , Wang Xiaozhong A. , Vafabakhsh Reza
Published: September 2023

During cell division, precise and regulated distribution of cellular material between daughter cells is a critical step and is governed by complex biochemical and biophysical mechanisms. To achieve this, membraneless organelles and condensates often require complete disassembly during mitosis. The biophysical principles governing the disassembly of condensates remain poorly understood. Here, we used a physical biology approach to study how physical and material properties of the nucleolus, a prominent nuclear membraneless organelle in eukaryotic cells, change during mitosis and across different scales. We found that nucleolus disassembly proceeds continuously through two distinct phases with a slow and reversible preparatory phase followed by a rapid irreversible phase that was concurrent with the nuclear envelope breakdown. We measured microscopic properties of nucleolar material including effective diffusion rates and binding affinities as well as key macroscopic properties of surface tension and bending rigidity. By incorporating these measurements into the framework of critical phenomena, we found evidence that near mitosis surface tension displays a power-law behavior as a function of biochemically modulated interaction strength. This two-step disassembly mechanism, which maintains structural and functional stability of nucleolus while allowing for its rapid and efficient disassembly in response to cell cycle cues, may be a universal design principle for the disassembly of other biomolecular condensates.
Evolutionary patterns and heterogeneity of Dengue Virus serotypes in Pakistan
Authors: Mumtaz Zilwa , Saif Rashid , Yousaf Muhammad Zubair
Published: September 2023

Comprehensive and systematic examination of Dengue virus (DENV) evolution is essential in the context of Pakistan as the virus presents a significant public health challenge with the ability to adapt and evolve. To shed light on intricate evolutionary patterns of all four DENV serotypes, we analyzed complete genome sequences (n=43) and envelope (E) gene sequences (n=44) of all four DENV serotypes collected in Pakistan from 1994 to 2023 providing a holistic view of their genetic evolution. Our findings revealed that all four serotypes of DENV co-circulate in Pakistan with a close evolutionary relationship between DENV-1 and DENV-3. Genetically distinct serotypes DENV-2 and DENV-4 indicate that DENV–4 stands out as the most genetically different, while DENV-2 exhibits greater complexity due to the presence of multiple genotypes and the possibility of temporal fluctuations in genotype prevalence. Selective pressure analysis in Envelope (E) gene revealed heterogeneity among sequences (n=44) highlighting 46 codons in the genome experiencing selective pressure, characterized by a bias towards balancing selection indicating genetic stability of the virus. Furthermore, our study suggested an intriguing evolutionary shift of DENV-4 towards the DENV-2 clade, potentially influenced by antibodies with cross-reactivity to multiple serotypes providing a critical insight into the complex factors shaping DENV evolution and contributing to the emergence of new serotype.

Author Summary

The emergence of the fifth serotype of dengue virus heightened our interest in investigating its presence in Pakistan. In our quest to understand the evolving landscape of dengue in Pakistan, we conducted a comprehensive analysis, comparing whole genome sequences and E gene sequences. Notably, we focused on the E gene recognized as the most mutable component and a key determinant of dengue’s virulence. The phylogenetic analysis unveiled fascinating findings, demonstrating a strong genetic affinity between serotypes 1 and 3. Substantially signifying its implications for vaccine development and understanding of cross-immunity dynamics within serotypes. We delved into the genetic dynamics of dengue by subjecting the whole genome of DENV and E gene to neutrality tests. The outcomes of these tests unveiled a critical aspect of dengue virus evolution: the genome is not evolving neutrally. Instead, the E gene experiences selective pressure, indicating a bias towards balancing selection. The finding underscores the complex interplay of factors shaping the genetic diversity of dengue in Pakistan and provides valuable insights into the virus’s adaptive strategies.
Identification of host factors for Rift Valley Fever Phlebovirus
Authors: Balaraman Velmurugan , Indran Sabarish V. , Li Yonghai , Meekins David A. , Jakkula Laxmi U.M.R. , Liu Heidi , Hays Micheal P. , Souza-Neto Jayme A. , Gaudreault Natasha N. , Hardwidge Philip R. , Wilson William C. , Weber Friedemann , Richt Juergen A.
Published: September 2023

Background

Rift Valley fever phlebovirus (RVFV) is a zoonotic pathogen that causes Rift Valley fever (RVF) in livestock and humans. Currently, there is no licensed human vaccine or antiviral drug to control RVF. Although multiple species of animals and humans are vulnerable to RVFV infection, host factors affecting susceptibility are not well understood.

Methodology

To identify the host factors or genes essential for RVFV replication, we conducted a CRISPR-Cas9 knock-out screen in human A549 cells. We then validated the putative genes using siRNA-mediated knockdowns and CRISPR-Cas9-mediated knockout studies, respectively. The role of a candidate gene in the virus replication cycle was assessed by measuring intracellular viral RNA accumulation, and the virus titers by plaque assay or TCID50assay.

Findings

We identified approximately 900 genes with potential involvement in RVFV infection and replication. Further evaluation of the effect of six genes on viral replication using siRNA-mediated knockdowns found that silencing two genes (WDR7 and LRP1) significantly impaired RVFV replication. For further analysis, we focused on theWDR7gene since the role ofLRP1in RVFV replication was previously described in detail. Knock-out A549 cell lines were generated and used to dissect the effect ofWRD7on RVFV and another bunyavirus, La Crosse encephalitis virus (LACV). We observed significant effects ofWDR7knock-out cells on both intracellular RVFV RNA levels and viral titers. At the intracellular RNA level,WRD7affected RVFV replication at a later phase of its replication cycle (24h) when compared to LACV which was affected an earlier replication phase (12h).

Conclusion

In summary, we have identifiedWDR7as an essential host factor for the replication of two relevant bunyaviruses, RVFV and LACV. Future studies will investigate the mechanistic role by whichWDR7facilitates Phlebovirus replication.

Authors Summary

Rift Valley fever phlebovirus is a high consequence pathogen that infects multiple animal species and also humans. Currently, there are no control measures available to treat RVF in humans and to prevent the incursion of Rift Valley fever virus into non-endemic countries. RVFV poses a significant threat to animal and human health in countries where it is endemic. RVFV replication depends on the host’s machinery to complete its replication cycle. Therefore, one way to control virus replication is to disrupt the interaction between the virus and the host proteins important for replication. In this study, we identified a host factor, the WDR7 gene, that is critical for RVFV replication. The identification of this host factor is important as it can potentially lead to the development of antiviral strategies to control Rift Valley fever in both humans and animals.
Organic matter degradation in the deep, sulfidic waters of the Black Sea: Insights into the ecophysiology of novel anaerobic bacteria
Authors: Yadav Subhash , Koenen Michel , Bale Nicole J , Reitsma Wietse , Engelmann Julia C , Damsté Jaap S. Sinninghe , Villanueva Laura
Published: September 2023

Our knowledge about the physiology of deep sea (>1,000 m) microorganisms involved in organic matter (OM) degradation is still scare due to the lack of available isolates, especially from sulfidic environments. In this study, we successfully cultivated and characterized the physiology of a wide range of novel piezotolerant anaerobic bacteria affiliated with the phylaFusobacteriota,Bacillota,Spirochaetota,Bacteroidota,Cloacimonadota,Planctomycetota,MycoplasmatotaandChloroflexotainvolved in OM degradation in deep sulfidic waters of the Black Sea. The novel taxa are specialized in degrading specific types of OM and cover a wide range of physiological categories, including primary degraders, fermenters, and terminal oxidizers. This is the first report which demonstrates this for such a diverse physiological group from any sulfidic marine habitat. Collectively, this study provides a step forward in our understanding of the microbes thriving in the extreme conditions of the deep sulfidic waters of the Black Sea.
A resource for probing influences of perinatal factors on neurodevelopment in 3-10-years-old Chinese children
Authors: Wang Yin-Shan , Su Xue-Ting , Ke Li , He Qing-Hua , Chang Da , Nie JingJing , Luo XinLi , Chen Fumei , Xu Jihong , Zhang Cai , Zhang Shudong , Zhang Shuyue , An Huiping , Guo Rui , Yue Suping , Duan Wen , Jia Shichao , Yang Sijia , Yu Yankun , Zhao Yang , Zhou Yang , Chen Li-Zhen , Fan Xue-Ru , Gao Peng , Lv Chenyu , Wu Ziyun , Zhao Yunyan , Quan Xi , Zhao Feng , Mu Yanchao , Yan Yu , Xu Wenchao , Liu Jie , Xing Lixia , Chen Xiaoqin , Wu Xiang , Zhao Lanfeng , Huang Zhijuan , Ren Yanzhou , Hao Hongyan , Li Hui , Wang Jing , Dong Qing , Chen Yanli , Huang Ruiwang , Liu Siman , Wang Yun , Dong Qi , Zuo Xi-Nian
Published: September 2023

Adverse perinatal factors can disrupt the normal development of the brain, with potential long-term impacts on children’s overall development. Currently, the neuropathological mechanisms by which these factors lead to various neurodevelopmental disorders (NDDs) remain largely unknown. An open resource that integrate perinatal factors with brain and mental health development is essential for investigating NDD-related aetiology. In this Data Descriptor, we introduce a multicentre database containing information on perinatal factors that influence children’s brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors associated with a high incidence of NDDs at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development among children aged 3–10 years are associated with perinatal factors. Ultimately, our goal was to develop an early prediction and screening model for NDDs that leverages normative data to facilitate NDD aetiology research. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD and present preliminary brain-mind associations.
BRG1/BRM inhibitor targets AML stem cells and exerts superior preclinical efficacy combined with BET or Menin inhibitor
Authors: Fiskus Warren , Piel Jessica , Collins Mike , Hentemann Murphy , Cuglievan Branko , Mill Christopher P. , Birdwell Christine E. , Das Kaberi , Davis John A. , Hou Hanxi , Jain Antrix , Malovannaya Anna , Kadia Tapan M. , Daver Naval , Sasaki Koji , Takahashi Koichi , Hammond Danielle , Reville Patrick , Wang Jian , Loghavi Sanam , Sen Rwik , Ruan Xinjia , Su Xiaoping , Flores Lauren B. , DiNardo Courtney D. , Bhalla Kapil N.
Published: October 2023

BRG1 (SMARCA4) and BRM (SMARCA2) are the core ATPases of chromatin remodeling BAF (BRG1/BRM-associated factor) complexes, which enable transcription factors/co-factors to modulate gene-expressions, mediating growth, differentiation-arrest and survival of AML cells. In AML with MLL1r (MLL1 rearrangement) or mutant (mt) NPM1, although monotherapy with Menin inhibitor (MI) induces clinical remissions, most patients either fail to respond or relapse. FHD-286 is a selective BRG1/BRM inhibitor, undergoing clinical development in AML. Here, FHD-286 induced differentiation and lethality in AML cells with MLL1r or mtNPM1, reducing chromatin accessibility and repressing c-Myc, PU.1 and CDK4/6. Whereas FHD-286 monotherapy reduced AML burden, leukemia-initiating potential and improved survival, FHD-286 combinations with MI, BET inhibitor, decitabine or venetoclax was significantly more effective in reducing AML burden and improved survival, without significant toxicity, in xenograft models of AML with MLL1r or mtNPM1. These findings highlight promising FHD-286-based combinations for therapy of AML with MLL1r or mtNPM1.

Statement of Significance

Inhibition of BRG1/BRM ATPases by FHD-286 reduced chromatin accessibility, repressed c-Myc, PU.1 and CDK4/6, inducing differentiation, leukemia-initiating potential and lethality in AML stem-progenitor cells. FHD-286-based combinations with Menin or BET inhibitor or decitabine reduced AML burden and improved survival in xenograft models of AML with MLL rearrangement or mutant NPM1.
Transcriptome-wide RNA structure probing with temporal resolution
Authors: Wang Danyang , Tang Yongkang , Li Ang , Sun Lei , Kleiner Ralph E.
Published: September 2023

Reactive small-molecule probes are widely used for RNA structure probing, however current approaches largely measure average RNA transcript dynamics and do not resolve structural differences that occur during folding or transcript maturation. Here, we present SNIPER-seq, an RNA structure probing method relying upon metabolic labeling with 2’-aminodeoxycytidine, structure-dependent 2’-amino reaction with an aromatic isothiocyanate, and high-throughput RNA sequencing. Our method maps cellular RNA structure transcriptome-wide with temporal resolution enabling determination of transcript age-dependent RNA structural dynamics. We benchmark our approach against known RNA structures and investigate the dynamics of human 5S rRNA during ribosome biogenesis, revealing specific structural changes in 5S rRNA loops that occur over the course of several hours. Taken together, our work sheds light on the maturation and coordinated conformational changes that take place during ribosome biogenesis and provides a general strategy for surveying evolving RNA structural dynamics across the transcriptome.