bluuebunny/crossref_metadata_2025 huggingface dataset:
Strengths-Based Factors Related to Post-Traumatic Stress Problems in Black Youth with High Body Weights
Authors: Campbell Kaytryn D , Howell Kathryn H , Napier Taylor R , Maye Caitlyn , Thurston Idia B
Published: June 2023

Objective

Black youth with high body weights [BYHW; Body Mass Index (BMI)≥95th percentile] endure unique stressors (e.g., exposure to discrimination due to race and size) that may contribute to psychopathology. Factors that decrease mental health problems associated with these stressors have been underexamined in BYHW. The current study assessed how multisystemic resilience, weight-related quality of life (QOL), and discrimination were associated with post-traumatic stress problems in BYHW from the perspective of youth and their caregivers.

Methods

A total of 93 BYHW and one of their primary caregivers were recruited from a Midsouth children’s hospital. Youth ranged in age from 11 to 17 years (Mage=13.94, SD = 1.89), were mostly girls (61.3%), and had CDC-defined BMI scores above the 95th percentile. Nearly all caregivers were mothers (91.4%; Mage=41.73 years, SD = 8.08). Youth and their caregivers completed measures of resilience, discrimination, weight-related QOL, and post-traumatic stress problems.

Results

Utilizing linear regression modeling, the youth model was significant [F(3, 89)=31.63, p<.001, Adj. R2=.50], with higher resilience (β=−.23; p=.01) and lower discrimination (β=.52; p<.001) associated with fewer post-traumatic stress problems. The caregiver regression model was also significant [F(2, 90)=10.45, p<.001, Adj. R2=.17], with higher weight-related QOL associated with lower post-traumatic stress problems (β=−.37; p<.001).

Conclusions

Findings illustrate differences in youth and caregiver perceptions of factors related to post-traumatic stress problems in BYHW. Youth emphasized both internal and external contributors to stress, while caregivers focused on internal variables. Such knowledge could be harnessed to develop strengths-based interventions that address health and well-being among BYHW.
Small area estimation under a spatially correlated multivariate area-level model
Authors: Guha Saurav , Chandra Hukum
Published: June 2023

Spatial version of multivariate Fay–Herriot model is introduced and small area predictor under this model is proposed. The residual maximum likelihood is employed for estimating the parameters of the proposed model. Analytical and bootstrap approaches for estimating the mean squared error (MSE) of the proposed predictor are also developed. The performance of the proposed predictor and the MSE estimators are evaluated through various simulation studies. The results evidently show that the proposed predictor outperforms the existing predictors. An application of the proposed methodology has also been made using the 2011–12 Consumer Expenditure Survey data of India.
A case of cutaneous psoriasis vulgaris achieving complete remission post major breast reconstructive surgery
Authors: Ngiam Erica Hian Kim , Fok Denise , Sim Nadia , Wong Allen , Feng Jiajun , Pearlie Tan , Chua Hui Wen , Chan Grace , Kok Yee Onn
Published: June 2023

Psoriasis is a debilitating chronic inflammatory systemic condition largely affecting the skin. Major surgery is relatively contraindicated due to the propensity for triggering psoriatic flares and koebnerization of the surgical scars. We detail an interesting case of complete psoriasis remission following a right nipple-sparing mastectomy with sentinel lymph node biopsy with vascular augmented pedicled transverse rectus abdominal myocutaneous (TRAM) flap in a patient with systemic psoriasis vulgaris and arthropathy. Intra-operatively, majority of the psoriatic plaques were excised or de-epithelized and used as part of the ipsilateral TRAM flap. Post-operatively, koebnerization did not occur and her psoriasis was cured completely even after cancer chemotherapy. One of several hypotheses include excision with de-epithelization of most of the psoriatic plaques reduces disease and inflammatory burden leading to complete remission. Perhaps, surgery could one day play a supporting role to existing treatment options to achieve psoriasis remission.
Defining drivers of under-immunization and vaccine hesitancy in refugee and migrant populations
Authors: Deal Anna , Crawshaw Alison F , Carter Jessica , Knights Felicity , Iwami Michiyo , Darwish Mohammad , Hossain Rifat , Immordino Palmira , Kaojaroen Kanokporn , Severoni Santino , Hargreaves Sally
Published: June 2023

Background/objective

Some refugee and migrant populations globally showed lower uptake of COVID-19 vaccines and are also considered to be an under-immunized group for routine vaccinations. These communities may experience a range of barriers to vaccination systems, yet there is a need to better explore drivers of under-immunization and vaccine hesitancy in these mobile groups.

Methods

We did a global rapid review to explore drivers of under-immunization and vaccine hesitancy to define strategies to strengthen both COVID-19 and routine vaccination uptake, searching MEDLINE, Embase, Global Health PsycINFO and grey literature. Qualitative data were analysed thematically to identify drivers of under-immunization and vaccine hesitancy, and then categorized using the ‘Increasing Vaccination Model’.

Results

Sixty-three papers were included, reporting data on diverse population groups, including refugees, asylum seekers, labour migrants and undocumented migrants in 22 countries. Drivers of under-immunization and vaccine hesitancy pertaining to a wide range of vaccines were covered, including COVID-19 (n = 27), human papillomavirus (13), measles or Measles-mumps-rubella (MMR) (3), influenza (3), tetanus (1) and vaccination in general. We found a range of factors driving under-immunization and hesitancy in refugee and migrant groups, including unique awareness and access factors that need to be better considered in policy and service delivery. Acceptability of vaccination was often deeply rooted in social and historical context and influenced by personal risk perception.

Conclusions

These findings hold direct relevance to current efforts to ensure high levels of global coverage for a range of vaccines and to ensure that marginalized refugee and migrant populations are included in the national vaccination plans of low-, middle- and high-income countries. We found a stark lack of research from low- and middle-income and humanitarian contexts on vaccination in mobile groups. This needs to be urgently rectified if we are to design and deliver effective programmes that ensure high coverage for COVID-19 and routine vaccinations.
A Century and a Quarter of Hoyle
Authors: Levy David
Published: June 2023

Edmond Hoyle wrote the first instructional books on the strategy for card play in the 1740s. The copyright owners, the Proprietors, published them successfully as Hoyle’s Games for a generation. The 1774 decision in Donaldson v Beckett invalidated the copyright and the Proprietors faced legal competition for the first time. Competing booksellers published innovative gaming manuals, marketing them as improved versions of Hoyle, with clearer prose, treatment of additional games, and new formats.

Despite the loss of copyright protection and the resulting competition, an ever-changing group of Proprietors dominated the market for gaming literature until the 1860s. With a bibliographical examination of the books, supplemented by archival records of the book trade, this article documents the Proprietor’s success and the reasons for it. The study provides a nuanced perspective of the impact of the Donaldson decision on an unfamiliar genre of literature.
Five nucleotides found in RCTG motifs are essential for post-fertilization methylation imprinting of the H19 ICR in YAC transgenic mice
Authors: Matsuzaki Hitomi , Takahashi Takuya , Kuramochi Daichi , Hirakawa Katsuhiko , Tanimoto Keiji
Published: June 2023

Genomic imprinting at the mouse Igf2/H19 locus is controlled by the H19 ICR, within which paternal allele-specific DNA methylation originating in sperm is maintained throughout development in offspring. We previously found that a 2.9 kb transgenic H19 ICR fragment in mice can be methylated de novo after fertilization only when paternally inherited, despite its unmethylated state in sperm. When the 118 bp sequence responsible for this methylation in transgenic mice was deleted from the endogenous H19 ICR, the methylation level of its paternal allele was significantly reduced after fertilization, suggesting the activity involving this 118 bp sequence is required for methylation maintenance at the endogenous locus. Here, we determined protein binding to the 118 bp sequence using an in vitro binding assay and inferred the binding motif to be RCTG by using a series of mutant competitors. Furthermore, we generated H19 ICR transgenic mice with a 5-bp substitution mutation that disrupts the RCTG motifs within the 118 bp sequence, and observed loss of methylation from the paternally inherited transgene. These results indicate that imprinted methylation of the H19 ICR established de novo during the post-fertilization period involves binding of specific factors to distinct sequence motifs within the 118 bp sequence.
Mutation signature filtering enables high-fidelity RNA structure probing at all four nucleobases with DMS
Authors: Mitchell David , Cotter Jennifer , Saleem Irfana , Mustoe Anthony M
Published: June 2023

Chemical probing experiments have transformed RNA structure analysis, enabling high-throughput measurement of base-pairing in living cells. Dimethyl sulfate (DMS) is one of the most widely used structure probing reagents and has played a pivotal role in enabling next-generation single-molecule probing analyses. However, DMS has traditionally only been able to probe adenine and cytosine nucleobases. We previously showed that, using appropriate conditions, DMS can also be used to interrogate base-pairing of uracil and guanines in vitro at reduced accuracy. However, DMS remained unable to informatively probe guanines in cells. Here, we develop an improved DMS mutational profiling (MaP) strategy that leverages the unique mutational signature of N1-methylguanine DMS modifications to enable high-fidelity structure probing at all four nucleotides, including in cells. Using information theory, we show that four-base DMS reactivities convey greater structural information than current two-base DMS and SHAPE probing strategies. Four-base DMS experiments further enable improved direct base-pair detection by single-molecule PAIR analysis, and ultimately support RNA structure modeling at superior accuracy. Four-base DMS probing experiments are straightforward to perform and will broadly facilitate improved RNA structural analysis in living cells.
Structural and biochemical insights into the molecular mechanism of TRPT1 for nucleic acid ADP-ribosylation
Authors: Yang Xiaoyun , Wang Jiaxu , Li Simin , Li Xiaobing , Gong Jingjing , Yan Zhenzhen , Zhou Huan , Wu Chen , Liu Xiuhua
Published: June 2023

Nucleic acid ADP-ribosylation has been established as a novel modification found in a wide diversity of prokaryotic and eukaryotic organisms. tRNA 2′-phosphotransferase 1 (TRPT1/TPT1/KptA) possesses ADP-ribosyltransferase (ART) activity and is able to ADP-ribosylate nucleic acids. However, the underlying molecular mechanism remains elusive. Here, we determined crystal structures of TRPT1s in complex with NAD+ from Homo sapiens, Mus musculus and Saccharomyces cerevisiae. Our results revealed that the eukaryotic TRPT1s adopt common mechanisms for both NAD+ and nucleic acid substrate binding. The conserved SGR motif induces a significant conformational change in the donor loop upon NAD+ binding to facilitate the catalytic reaction of ART. Moreover, the nucleic acid-binding residue redundancy provides structural flexibility to accommodate different nucleic acid substrates. Mutational assays revealed that TRPT1s employ different catalytic and nucleic acid-binding residues to perform nucleic acid ADP-ribosylation and RNA 2′-phosphotransferase activities. Finally, cellular assays revealed that the mammalian TRPT1 is able to promote endocervical HeLa cell survival and proliferation. Together, our results provide structural and biochemical insights into the molecular mechanism of TRPT1 for nucleic acid ADP-ribosylation.
Pyrimidine catabolism is required to prevent the accumulation of 5-methyluridine in RNA
Authors: Gao Shangyu , Sun Yu , Chen Xiaoguang , Zhu Changhua , Liu Xiaoye , Wang Wenlei , Gan Lijun , Lu Yanwu , Schaarschmidt Frank , Herde Marco , Witte Claus-Peter , Chen Mingjia
Published: June 2023

5-Methylated cytosine is a frequent modification in eukaryotic RNA and DNA influencing mRNA stability and gene expression. Here we show that free 5-methylcytidine (5mC) and 5-methyl-2′-deoxycytidine are generated from nucleic acid turnover in Arabidopsis thaliana, and elucidate how these cytidines are degraded, which is unclear in eukaryotes. First CYTIDINE DEAMINASE produces 5-methyluridine (5mU) and thymidine which are subsequently hydrolyzed by NUCLEOSIDE HYDROLASE 1 (NSH1) to thymine and ribose or deoxyribose. Interestingly, far more thymine is generated from RNA than from DNA turnover, and most 5mU is directly released from RNA without a 5mC intermediate, since 5-methylated uridine (m5U) is an abundant RNA modification (m5U/U ∼1%) in Arabidopsis. We show that m5U is introduced mainly by tRNA-SPECIFIC METHYLTRANSFERASE 2A and 2B. Genetic disruption of 5mU degradation in the NSH1 mutant causes m5U to occur in mRNA and results in reduced seedling growth, which is aggravated by external 5mU supplementation, also leading to more m5U in all RNA species. Given the similarities between pyrimidine catabolism in plants, mammals and other eukaryotes, we hypothesize that the removal of 5mU is an important function of pyrimidine degradation in many organisms, which in plants serves to protect RNA from stochastic m5U modification.
Evaluating Survival After Hospitalization Due to Immune-Related Adverse Events From Checkpoint Inhibitors
Authors: Silverstein Jordyn , Wright Francis , Wang Michelle , Young Arabella , Kim Daniel , De Dios Kimberly , Brondfield Sam , Quandt Zoe
Published: June 2023

Background

As immune checkpoint inhibitors (CPI) are increasingly approved for cancer treatment, hospitalizations related to severe immune-related adverse events (irAE) will increase. Here, we identify patients hospitalized due to irAEs and describe survival outcomes across irAE, CPI, and cancer type.

Methods

We identified patients hospitalized at our institution from January 2012 to December 2020 due to irAEs. Survival was analyzed using Kaplan-Meier survival curves with log-rank tests.

Results

Of 3137 patients treated with CPIs, 114 (3.6%) were hospitalized for irAEs, resulting in 124 hospitalizations. Gastrointestinal (GI)/hepatic, endocrine, and pulmonary irAEs were the most common causes of irAE-related hospitalization. After CPI initiation, the average time to hospitalization was 141 days. Median survival from hospital admission was 980 days. Patients hospitalized due to GI/hepatic and endocrine irAEs had longer median survival than patients with pulmonary irAEs (795 and 949 days vs. 83 days [P < .001]). Patients with melanoma and renal cell carcinoma had longer median survival than patients with lung cancer (2792 days and not reached vs. 159 days [P < .001]). There was longer median survival in the combination group compared to the PD-(L)1 group (1471 vs. 529 days [P = .04]).

Conclusions

As CPI use increases, irAE-related hospitalizations will as well. These findings suggest that among patients hospitalized for irAEs, survival differs by irAE and cancer type, with worse survival for patients with irAE pneumonitis or lung cancer. This real-world data contributes to research pertaining to hospitalization due to severe irAEs, which may inform patient counseling and treatment decision-making.
Health Equity in Patients Receiving Durvalumab for Unresectable Stage III Non-Small Cell Lung Cancer in the US Veterans Health Administration
Authors: Moore Amanda M , Nooruddin Zohra , Reveles Kelly R , Koeller Jim M , Whitehead Jennifer M , Franklin Kathleen , Datta Paromita , Alkadimi Munaf , Brannman Lance , Cotarla Ion , Frankart Andrew J , Mulrooney Tiernan , Jones Xavier , Frei Christopher R
Published: June 2023

Background

Real-world evidence is limited regarding the relationship between race and use of durvalumab, an immunotherapy approved for use in adults with unresectable stage III non-small cell lung cancer (NSCLC) post-chemoradiotherapy (CRT). This study aimed to evaluate if durvalumab treatment patterns differed by race in patients with unresectable stage III NSCLC in a Veterans Health Administration (VHA) population.

Materials and Methods

This was a retrospective analysis of White and Black adults with unresectable stage III NSCLC treated with durvalumab presenting to any VHA facility in the US from January 1, 2017, to June 30, 2020. Data captured included baseline characteristics and durvalumab treatment patterns, including treatment initiation delay (TID), interruption (TI), and discontinuation (TD); defined as CRT completion to durvalumab initiation greater than 42 days, greater than 28 days between durvalumab infusions, and more than 28 days from the last durvalumab dose with no new durvalumab restarts, respectively. The number of doses, duration of therapy, and adverse events were also collected.

Results

A total of 924 patients were included in this study (White = 726; Black = 198). Race was not a significant factor in a multivariate logistic regression model for TID (OR, 1.39; 95% CI, 0.81-2.37), TI (OR, 1.58; 95% CI, 0.90-2.76), or TD (OR, 0.84; 95% CI, 0.50-1.38). There were also no significant differences in median (interquartile range [IQR]) number of doses (White: 15 [7-24], Black: 18 [7-25]; P = .25) or median (IQR) duration of therapy (White: 8.7 months [2.9-11.8], Black: 9.8 months [3.6-12.0]; P = .08), although Black patients were less likely to experience an immune-related adverse event (28% vs. 36%, P = .03) and less likely to experience pneumonitis (7% vs. 14%, P < .01).

Conclusion

Race was not found to be linked with TID, TI, or TD in this real-world study of patients with unresectable stage III NSCLC treated with durvalumab at the VHA.
Arabidopsis lamin-like proteins CRWN1 and CRWN2 interact with SUPPRESSOR OF NPR1-1 INDUCIBLE 1 and RAD51D to prevent DNA damage
Authors: Yin Chunmei , Sun Aiqing , Guo Tongtong , Mao Xuegao , Fang Yuda
Published: June 2023

Plants cope with various recurring stress conditions that often induce DNA damage, ultimately affecting plant genome integrity, growth, and productivity. The CROWDED NUCLEI (CRWN) family comprises lamin-like proteins with multiple functions, such as regulating gene expression, genome organization, and DNA damage repair in Arabidopsis (Arabidopsis thaliana). However, the mechanisms and consequences of CRWNs in DNA damage repair are largely unknown. Here, we reveal that CRWNs maintain genome stability by forming repairing nuclear bodies at DNA double-strand breaks. We demonstrate that CRWN1 and CRWN2 physically associate with the DNA damage repair proteins RAD51D and SUPPRESSOR OF NPR1-1 Inducible 1 (SNI1) and act in the same genetic pathway to mediate this process. Moreover, CRWN1 and CRWN2 partially localize at γ-H2AX foci upon DNA damage. Notably, CRWN1 and CRWN2 undergo liquid–liquid phase separation to form highly dynamic droplet-like structures with RAD51D and SNI1 to promote the DNA damage response (DDR). Collectively, our data shed light on the function of plant lamin-like proteins in the DDR and maintenance of genome stability.
MYB112 connects light and circadian clock signals to promote hypocotyl elongation in Arabidopsis
Authors: Cai Yupeng , Liu Yongting , Fan Yangyang , Li Xitao , Yang Maosheng , Xu Dongqing , Wang Haiyang , Deng Xing Wang , Li Jian
Published: June 2023

Ambient light and the endogenous circadian clock play key roles in regulating Arabidopsis (Arabidopsis thaliana) seedling photomorphogenesis. PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) acts downstream of both light and the circadian clock to promote hypocotyl elongation. Several members of the R2R3-MYB transcription factor (TF) family, the most common type of MYB TF family in Arabidopsis, have been shown to be involved in regulating photomorphogenesis. Nonetheless, whether R2R3-MYB TFs are involved in connecting the light and clock signaling pathways during seedling photomorphogenesis remains unknown. Here, we report that MYB112, a member of the R2R3-MYB family, acts as a negative regulator of seedling photomorphogenesis in Arabidopsis. The light signal promotes the transcription and protein accumulation of MYB112. myb112 mutants exhibit short hypocotyls in both constant light and diurnal cycles. MYB112 physically interacts with PIF4 to enhance the transcription of PIF4 target genes involved in the auxin pathway, including YUCCA8 (YUC8), INDOLE-3-ACETIC ACID INDUCIBLE 19 (IAA19), and IAA29. Furthermore, MYB112 directly binds to the promoter of LUX ARRHYTHMO (LUX), the central component of clock oscillators, to repress its expression mainly in the afternoon and relieve LUX-inhibited expression of PIF4. Genetic evidence confirms that LUX acts downstream of MYB112 in regulating hypocotyl elongation. Thus, the enhanced transcript accumulation and transcriptional activation activity of PIF4 by MYB112 additively promotes the expression of auxin-related genes, thereby increasing auxin synthesis and signaling and fine-tuning hypocotyl growth under diurnal cycles.
Inhibitor AN3661 reveals biological functions of Arabidopsis CLEAVAGE and POLYADENYLATION SPECIFICITY FACTOR 73
Authors: Hao Saiqi , Zhang Lidan , Zhao Danhui , Zhou Jiawen , Ye Congting , Qu Haidong , Li Qingshun Q
Published: June 2023

Cleavage and polyadenylation specificity factor (CPSF) is a protein complex that plays an essential biochemical role in mRNA 3′-end formation, including poly(A) signal recognition and cleavage at the poly(A) site. However, its biological functions at the organismal level are mostly unknown in multicellular eukaryotes. The study of plant CPSF73 has been hampered by the lethality of Arabidopsis (Arabidopsis thaliana) homozygous mutants of AtCPSF73-I and AtCPSF73-II. Here, we used poly(A) tag sequencing to investigate the roles of AtCPSF73-I and AtCPSF73-II in Arabidopsis treated with AN3661, an antimalarial drug with specificity for parasite CPSF73 that is homologous to plant CPSF73. Direct seed germination on an AN3661-containing medium was lethal; however, 7-d-old seedlings treated with AN3661 survived. AN3661 targeted AtCPSF73-I and AtCPSF73-II, inhibiting growth through coordinating gene expression and poly(A) site choice. Functional enrichment analysis revealed that the accumulation of ethylene and auxin jointly inhibited primary root growth. AN3661 affected poly(A) signal recognition, resulted in lower U-rich signal usage, caused transcriptional readthrough, and increased the distal poly(A) site usage. Many microRNA targets were found in the 3′ untranslated region lengthened transcripts; these miRNAs may indirectly regulate the expression of these targets. Overall, this work demonstrates that AtCPSF73 plays important part in co-transcriptional regulation, affecting growth, and development in Arabidopsis.
Is there an association between serum soluble interleukin-2 receptor levels and syndrome severity in persistent Complex Regional Pain Syndrome?
Authors: Mangnus Thomas J P , Bharwani Krishna D , Dik Willem A , Baart Sara J , Dirckx Maaike , Huygen Frank J P M
Published: June 2023

Objective

A potentially useful biomarker for Complex Regional Pain Syndrome (CRPS) is the serum soluble interleukin-2 receptor (sIL-2R) level, which is a marker for T-cell activation. Elevated serum sIL-2R levels have been described in CRPS patients compared to healthy controls. In T-cell mediated inflammatory diseases such as sarcoidosis and rheumatoid arthritis, the serum sIL-2R levels correlate with disease severity. In this study, we investigate whether an association exists between serum sIL-2R levels in CRPS patients and CRPS severity.

Methods

A cross-sectional cohort study was conducted in a tertiary pain referral center in the Netherlands. Adult CRPS patients diagnosed by the IASP criteria were included between October 2018 until October 2022. The main study parameters were serum sIL-2R levels and the CRPS severity score.

Results

Fifty-three CRPS patients were included with a mean syndrome duration of 84 months (Q3 − Q1:180 − 48). The majority had persistent CRPS with a syndrome duration >1 year (n = 52, 98%). The median pain Numerical Rating Score (NRS) was 7 (Q3 − Q1: 8 − 5) and the mean CRPS severity score was 11 (SD ± 2.3). The median serum sIL-2R level was 330 U/mL (Q3 − Q1:451 − 256). No statistically significant correlation was observed between serum sIL-2R levels and the CRPS severity score (rs = 0.15, P = .28).

Conclusions

Our findings suggest that serum sIL-2R levels cannot be used as a biomarker for syndrome severity in persistent CRPS (syndrome duration >1 year). Serial measurements of serum sIL-2R from early CRPS to persistent CRPS are needed to investigate whether serum sIL-2R levels can be used to monitor T-cell mediated inflammatory syndrome activity.
Emergent structural correlations in dense liquids
Authors: Pihlajamaa Ilian , Laudicina Corentin C L , Luo Chengjie , Janssen Liesbeth M C
Published: June 2023

The complete quantitative description of the structure of dense and supercooled liquids remains a notoriously difficult problem in statistical physics. Most studies to date focus solely on two-body structural correlations, and only a handful of papers have sought to consider additional three-body correlations. Here, we go beyond the state of the art by extracting many-body static structure factors from molecular dynamics simulations and by deriving accurate approximations up to the six-body structure factor via density functional theory. We find that supercooling manifestly increases four-body correlations, akin to the two- and three-body case. However, at small wave numbers, we observe that the four-point structure of a liquid drastically changes upon supercooling, both qualitatively and quantitatively, which is not the case in two-point structural correlations. This indicates that theories of the structure or dynamics of dense liquids should incorporate many-body correlations beyond the two-particle level to fully capture their intricate behavior.
A PITX2–HTR1B pathway regulates the asymmetric development of female gonads in chickens
Authors: Peng Zhelun , Man Qiu , Meng Lu , Wang Sheng , Cai Hao , Zhang Chuansheng , Li Xianyao , Wang Heng , Zhu Guiyu
Published: June 2023

All female vertebrates develop a pair of ovaries except for birds, in which only the left gonad develops into an ovary, whereas the right gonad regresses. Previous studies found that the transcription factor Paired-Like Homeodomain 2 (PITX2), a key mediator for left/right morphogenesis in vertebrates, was also implicated in asymmetric gonadal development in chickens. In this study, we systematically screened and validated the signaling pathways that could be targeted by Pitx2 to control unilateral gonad development. Integrated chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) analyses indicated that Pitx2 directly binds to the promoters of genes encoding neurotransmitter receptors and leads to left-biased expression of both serotonin and dopamine receptors. Forcibly activating serotonin receptor 5-Hydroxytryptamine Receptor 1B (HTR1B) signaling could induce ovarian gene expression and cell proliferation to partially rescue the degeneration of the right gonad. In contrast, inhibiting serotonin signaling could block the development of the left gonad. These findings reveal a PITX2–HTR1B genetic pathway that guides the left-specific ovarian growth in chickens. We also provided new evidence showing neurotransmitters stimulate the growth of nonneuronal cells during the early development of reproductive organs well before innervation.
Microfluidic platform using focused ultrasound passing through hydrophobic meshes with jump availability
Authors: Koroyasu Yusuke , Nguyen Thanh-Vinh , Sasaguri Shun , Marzo Asier , Ezcurdia Iñigo , Nagata Yuuya , Yamamoto Tatsuya , Nomura Nobuhiko , Hoshi Takayuki , Ochiai Yoichi , Fushimi Tatsuki
Published: June 2023

Applications in chemistry, biology, medicine, and engineering require the large-scale manipulation of a wide range of chemicals, samples, and specimens. To achieve maximum efficiency, parallel control of microlitre droplets using automated techniques is essential. Electrowetting-on-dielectric (EWOD), which manipulates droplets using the imbalance of wetting on a substrate, is the most widely employed method. However, EWOD is limited in its capability to make droplets detach from the substrate (jumping), which hinders throughput and device integration. Here, we propose a novel microfluidic system based on focused ultrasound passing through a hydrophobic mesh with droplets resting on top. A phased array dynamically creates foci to manipulate droplets of up to 300 μL. This platform offers a jump height of up to 10 cm, a 27-fold improvement over conventional EWOD systems. In addition, droplets can be merged or split by pushing them against a hydrophobic knife. We demonstrate Suzuki-Miyaura cross-coupling using our platform, showing its potential for a wide range of chemical experiments. Biofouling in our system was lower than in conventional EWOD, demonstrating its high suitability for biological experiments. Focused ultrasound allows the manipulation of both solid and liquid targets. Our platform provides a foundation for the advancement of micro-robotics, additive manufacturing, and laboratory automation.
The politics of COVID-19 experts: comparing winners and losers in Italy and the UK
Authors: Cairney Paul , Toth Federico
Published: June 2023

This article analyzes the “politics of experts”—or the struggle between scientific advisers to gain visibility and influence—in the early months of the COVID-19 pandemic in Italy and the UK. Modifying classic studies of policy communities of interest groups and civil servants, we classify relevant policy experts in the two countries into the following categories: “core insiders,” “specialist insiders,” “peripheral insiders,” and “outsiders.” Within these categories, we distinguish between “high-profile” and “low-profile” experts, depending on media exposure. The comparison between the UK and Italian cases helps to identify how actors interpret and follow formal and informal “rules of the game.” We identify a contest between experts to influence policy with reference to two competing “rules of the game.” The first set of rules comes from government, while the second comes from science advice principles. These rules collide, such as when governments require secrecy and nonconfrontation and scientists expect transparency and independent criticism. Therefore, experts face dilemmas regarding which rules to favor: some accept the limits to their behavior to ensure insider access; others are free to criticize the policies that they struggle to influence.
Myocarditis post–COVID-19 vaccination
Authors: Bansal Mridul , Mehta Aryan , Pandey Mandvi
Published: June 2023

There has been much interest in the possible adverse events associated with available anti–coronavirus disease of 2019 (COVID-19) vaccines, given the rapid pace at which they had to be developed during the pandemic. One such adverse event is myocarditis post–COVID-19 vaccination. Several pathophysiological mechanisms have been proposed that might help us understand the relationship between the messenger ribonucleic acid (mRNA) vaccine and the occurrence of myocarditis, though we are yet to ascertain the causal link between them. Although the actual absolute incidence of myocarditis post–COVID-19 vaccination remains low among the large, general population that has been vaccinated, there has been a high relative incidence of this adverse event. We aim to review the existing literature and bring to light what we have so far understood with respect to the association between COVID-19 vaccination and myocarditis. This will help in better understanding the burden of the pathology along with alleviating apprehensions associated with it.

Key messages
Comprehensive management of Jehovah’s Witness in pregnancy
Authors: Pang Fei San , Liaw Elvin Yee Fan , De Somsubhra
Published: June 2023

Jehovah’s Witness (JW) is a denomination of Christianity which has many-fold higher morbidity and mortality compared to the general population as they refuse blood transfusion. Information is scanty regarding guidelines on the optimal approach to pregnant ladies of JW faith. In this review we have attempted to analyse the ways and techniques available which can be used to reduce the morbidity and mortality of these women. In antenatal care, haematological status can be optimised to reduce modifiable risk factors, namely anaemia by parenteral iron therapy from the second trimester onwards especially in patients who do not respond to oral iron therapy. In severe cases, erythropoietin serves as an effective alternative to blood transfusion. During the intrapartum period, using antifibrinolytics, cell salvage, bloodless surgical techniques, and uterine cooling for patients undergoing caesarean delivery have been proven effective. To conclude, complications of pregnant JW patients may be reduced if they comply with the preventives and targeted monitoring during the various phases of pregnancy. Further studies are warranted as this population exists as a minor group but is growing worldwide.

Key messages

Current research questions
Biomimetic, biodegradable and osteoinductive treated dentin matrix/α-calcium sulphate hemihydrate composite material for bone tissue engineering
Authors: Guo Runying , Zhang Rui , Liu Sirui , Yang Yanyu , Dong Wenhang , Wang Meiyue , Mi Hongyan , Liu Mengzhe , Sun Jingjing , Zhang Xue , Su Yimeng , Liu Yiming , Huang Di , Li Rui
Published: June 2023

It is still a huge challenge for bone regenerative biomaterial to balance its mechanical, biological and biodegradable properties. In the present study, a new composite material including treated dentin matrix (TDM) and α-calcium sulphate hemihydrate (α-CSH) was prepared. The optimal composition ratio between TDM and α-CSH was explored. The results indicate that both components were physically mixed and structurally stable. Its compressive strength reaches up to 5.027 ± 0.035 MPa for 50%TDM/α-CSH group, similar to human cancellous bone tissues. Biological experiments results show that TDM/α-CSH composite exhibits excellent biocompatibility and the expression of osteogenic related genes and proteins (ALP, RUNX2, OPN) is significantly increased. In vivo experiments suggest that the addition of TDM for each group (10%, 30%, 50%) effectively promotes cell proliferation and osteomalacia. In addition, 50% of the TDM/α-CSH combination displays optimal osteoconductivity. The novel TDM/α-CSH composite is a good candidate for certain applications in bone tissue engineering.
Systemic pharmacological treatment of digital ulcers in systemic sclerosis: a systematic literature review
Authors: Ross Laura , Maltez Nancy , Hughes Michael , Schoones Jan W , Baron Murray , Chung Lorinda , Giuggioli Dilia , Moinzadeh Pia , Suliman Yossra A , Campochiaro Corrado , Allanore Yannick , Denton Christopher P , Distler Oliver , Frech Tracy , Furst Daniel E , Khanna Dinesh , Krieg Thomas , Kuwana Masataka , Matucci-Cerinic Marco , Pope Janet , Alunno Alessia
Published: June 2023

Objective

To evaluate the evidence concerning systemic pharmacological treatments for SSc digital ulcers (DUs) to inform the development of evidence-based treatment guidelines.

Methods

A systematic literature review of seven databases was performed to identify all original research studies of adult patients with SSc DUs. Randomized controlled trials (RCTs) and prospective longitudinal observational studies (OBSs) were eligible for inclusion. Data were extracted, applying the patient, intervention, comparison, outcome framework, and risk of bias (RoB) was assessed. Due to study heterogeneity, narrative summaries were used to present data.

Results

Forty-seven studies that evaluated the treatment efficacy or safety of pharmacological therapies were identified among 4250 references. Data from 18 RCTs of 1927 patients and 29 OBSs of 661 patients, at various RoB (total 2588 patients) showed that i.v. iloprost, phosphodiesterase-5 inhibitors and atorvastatin are effective for the treatment of active DUs. Bosentan reduced the rate of future DUs in two RCTs (moderate RoB) and eight OBSs at low to high RoB. Two small studies (moderate RoB) indicate that Janus kinase inhibitors may be effective for the treatment of active DUs, otherwise there are no data to support the use of immunosuppression or anti-platelet agents in the management of DUs.

Conclusion

There are several systemic treatments, across four medication classes, that are effective therapies for the management of SSc DUs. However, a lack of robust data means it is not possible to define the optimal treatment regimen for SSc DUs. The relatively low quality of evidence available has highlighted further areas of research need.
Subtherapeutic hydroxychloroquine concentration is associated with increased disease activity and greater organ damage in lupus
Authors: Kang Ji-Hyoun , Choi Sung-Eun , Park Dong-Jin , Lee Shin-Seok
Published: June 2023

Objective

To investigate the effects of the serum HCQ concentration on clinical manifestations, disease activity and organ damage in a longitudinal cohort of SLE patients.

Methods

The 338 SLE patients were assessed with respect to their demographic data, clinical and laboratory findings, Physician’s Global Assessment (PGA), adjusted mean SLEDAI-2000 (AMS) and SLICC Damage Index (SDI) annually for 5 consecutive years. Patients were divided into two groups according to their serum HCQ concentration at baseline: subtherapeutic (<500 ng/ml) and therapeutic (≥500 ng/ml) groups. The impact of the HCQ concentration on the clinical outcomes was evaluated in a longitudinal analysis using a generalized estimating equation (GEE).

Results

Of the 338 patients, 287 (84.9%) were in the subtherapeutic group at baseline. This group had a higher incidence of newly developed LN (P = 0.036) and had been prescribed higher mean and cumulative doses of prednisolone (P = 0.003 and P = 0.013, respectively) than the therapeutic group. In multivariable analyses based on GEE, the subtherapeutic group had a higher AMS score (β = 1.398, 95% CI 0.607, 2.189; P < 0.001), higher PGA score (β = 0.328, 95% CI 0.215, 0.441; P < 0.001) and higher SDI score (β = 0.366, 95% CI 0.061, 0.671; P = 0.019) across all 5 years.

Conclusion

The subtherapeutic HCQ concentration was associated with the development of new-onset LN, and had significant associations with disease activity and cumulative organ damage in SLE patients over time.
Viewpoint: Glucocorticoids in the treatment of rheumatoid arthritis: points to (re)consider
Authors: Boers Maarten
Published: June 2023

Glucocorticoids (prednisone) are essential in the treatment of RA and other autoimmune diseases. They are widely used, but treatment guidelines advise against. This viewpoint article explains why and suggests a way forward.
Evidence-neglect: addressing a barrier to UK health and climate policy ambitions
Authors: Marteau Theresa M
Published: June 2023

Scientific evidence is just one of many sources of information for policymakers. Neglecting this evidence is, however, an important feature of unsuccessful policy-making. Recent UK governments’ ambitions to improve the nation’s health and tackle climate change are—to varying degrees—off course. These include halving childhood obesity by 2030 and achieving net zero carbon emissions by 2050. Evidence on the interventions most likely to achieve these is well summarised but largely neglected in the policies supporting these ambitions. Two sets of factors contribute to this neglect: first, incentive structures for politicians that favour setting ambitious policy goals while disfavouring the effective policies needed to achieve them; second, political ideologies and interests that conflict with effective policies. Two changes could mitigate these factors: first, engaging citizens more in policy-making so that their interests dominate; second, increasing the accountability of politicians through legally binding systems for all stages of policy-making.
Effects of Seed Treatments and Yield Potential on Infected Soybean Seed
Authors: Haafke Alexandria J. , Kandel Yuba R. , Batzer Jean C. , Dangal Nabin K. , Mueller Daren S.
Published: June 2023

Diaporthe seed decay is an endemic disease throughout most soybean-growing regions. A major outbreak of Diaporthe seed decay occurred in 2018 in Iowa and other parts of the United States. The most prevalent fungi associated with this outbreak in Iowa were Diaporthe longicolla and D. caulivora. We established field experiments in 2019 and 2020 in two central Iowa locations to evaluate the effects of seed treatments and yield potential of Diaporthe-infected seed lots. Seed of the same variety but originating from different sources were categorized as “good” or “bad” seed depending on the percentage of Diaporthe-infected seed. Four seed treatments were tested, and results indicated that there were differences in plant stand, plant health (normalized difference vegetation index and canopy coverage) (both years), and yield (2019) between both seed lots. The good seed lot had about 9% greater yield than the bad seed lot ( P < 0.001), whereas the seed lots had similar yield in 2020 ( P = 0.822). Seed treatments improved stand, canopy greenness, and canopy coverage but did not affect yield in either year. For the yield potential experiment, there were minimal differences in plant health and no differences in yield between good and bad seed lots thinned to the same plant population in both years. These results suggest that Diaporthe-infected seed lots with lower germination and plant stand resulted in lower yield, and seed treatments can improve soybean stand, canopy greenness, and coverage. Additionally, Diaporthe-infected seed did not affect soybean growth and development or yield once plant stand was established.
How Theory Can Inform Practice: A Case of Easing Transition Into Residency
Authors: Meeuwissen Stephanie N.E. , Steinert Yvonne , Konopasky Abigail W. , Stalmeijer Renée E.
Published: June 2023

Health professions educators aim to optimally prepare trainees for future practice; educational theory can help reach this goal. Below we present an authentic case, I Just Need to Speak With My Eyes, that displays the significant struggles of transitioning into residency training. Using this case, we show how the application of 4 learning mechanisms described in Lave and Wenger’s1,2 theories of situated learning and communities of practice can help ease the transition into residency by addressing issues like self-questioning and emotional turmoil (see the colored boxes below). Situated learning refers to learning in everyday practice and highlights its fundamentally social nature as well as the progressive participation of the learner.1 Communities of practice builds on the notion of people learning from each other, viewing learning as a shared enterprise among a group of people with a common purpose.2
An Exploration of the Relationship Between Atrial Fibrillation and Obesity
Authors: Upadhyay Kiran , Frishman William H.
Published: June 2023

In the past 40 years, the prevalence of atrial fibrillation and obesity have skyrocketed. It has long been established that obesity can lead to adverse cardiovascular outcomes due to its myriad of effects on cardiovascular architecture, cardiovascular hemodynamics, and electrical conduction interference. The goal of this article is to explore the pathogenesis of atrial fibrillation in obese patients and examine the role of atrial enlargement, increased adipose deposits surrounding the pericardium, interstitial fibrosis, and inflammation in the development and worsening of atrial fibrillation in obese patients.
Pleomorphic Dermal Sarcoma With Metastasis to the Lung: A Case Report
Authors: Shafi Saba , Bechtel Mark , Contreras Carlo M. , Plaza Jose A.
Published: June 2023

Atypical fibroxanthoma and pleomorphic dermal sarcoma (PDS) are dermal malignant mesenchymal tumors that lie at the ends of the same disease spectrum. Clinically indistinguishable from atypical fibroxanthoma, PDS has a more aggressive course with significantly higher rate of local recurrence and metastases. Histological findings that favor a PDS include subcutaneous invasion, tumor necrosis, lymphovascular invasion, and/or perineural infiltration. Herein, we report a case of PDS with metastasis to the lung. Our report highlights the risk of local recurrence and metastatic spread in this cutaneous tumor and the importance of distinguishing this entity from its less aggressive counterpart.
Development of a Moral Resilience Collaborative Program During a Pandemic
Authors: Cole Linda , Mackavey Carole , Ramaswamy Padmavathy , Mullassery Daisy G. , Vincent Heather
Published: June 2023

Elevated psychological stress can lead to moral distress affecting health care workers and organizations affecting patient care, job satisfaction, and retention. A Moral Resilience Collaborative program was implemented through an academic partnership between a school of nursing and a rehabilitation facility to provide the health care workers in the facility the skills necessary for self-management of moral distress and move them toward moral resilience. Moral distress and resiliency were measured pre-implementation using the Measure of Moral Distress for Healthcare Professionals (MMD-HP) and Short Resiliency Survey (SRS), respectively. Unfortunately, postsurvey quantitative data collection failed due to COVID-19 surges though qualitative data obtained during debriefing sessions demonstrated effectiveness of the project. Based on debriefing comments and the preimplementation MMD-HP mean score and SRS decompression score, the staff in this facility experienced similar types of moral distress as those working in acute care or critical care settings. Even when resiliency programs are needed the most and readily available, patient care demands, a busy work environment, and external factors can hinder staff participation in such endeavors.
The Effect of Acupressure Applied to Patients With Multiple Sclerosis on Fatigue
Authors: Sungur Meltem , Ovayolu Nimet , Akçalı Aylin
Published: June 2023

This study was conducted in order to examine the effect of acupressure applied to patients with multiple sclerosis on fatigue. The patients meeting the inclusion criteria were assigned to intervention (n = 30) and control (n = 30) groups. The data of the study were collected using a questionnaire and the Fatigue Severity Scale. During the study, the control group received its routine treatment; on the other hand, the intervention group received routine treatment and also the certified researcher, receiving the acupressure training, applied acupressure to the intervention group by using the points Li4, ST36 and SP6 3 times a week for a total of 4 weeks. The postacupressure fatigue mean score was 5.2 ± 0.7 in the intervention group and 5.9 ± 0.7 in the control group, and there was a significant difference in the control and intervention groups in terms of postacupressure fatigue mean scores (P < .05). According to these results of the study, it can be recommended to provide acupressure training to patients with multiple sclerosis in order to decrease the fatigue associated with multiple sclerosis.