bluuebunny/crossref_metadata_2025 huggingface dataset:
Biallelic NUDT2 variants defective in mRNA decapping cause a neurodevelopmental disease
Authors: Husain Ralf A , Jiao Xinfu , Hennings J Christopher , Giesecke Jan , Palsule Geeta , Beck-Wödl Stefanie , Osmanović Dina , Bjørgo Kathrine , Mir Asif , Ilyas Muhammad , Abbasi Saad M , Efthymiou Stephanie , Dominik Natalia , Maroofian Reza , Houlden Henry , Rankin Julia , Pagnamenta Alistair T , Nashabat Marwan , Altwaijri Waleed , Alfadhel Majid , Umair Muhammad , Khouj Ebtissal , Reardon William , El-Hattab Ayman W , Mekki Mohammed , Houge Gunnar , Beetz Christian , Bauer Peter , Putoux Audrey , Lesca Gaetan , Sanlaville Damien , Alkuraya Fowzan S , Taylor Robert W , Mentzel Hans-Joachim , Hübner Christian A , Huppke Peter , Hart Ronald P , Haack Tobias B , Kiledjian Megerditch , Rubio Ignacio
Published: December 2023

Dysfunctional RNA processing caused by genetic defects in RNA processing enzymes has a profound impact on the nervous system, resulting in neurodevelopmental conditions. We characterized a recessive neurological disorder in 18 children and young adults from 10 independent families typified by intellectual disability, motor developmental delay and gait disturbance.

In some patients peripheral neuropathy, corpus callosum abnormalities and progressive basal ganglia deposits were present. The disorder is associated with rare variants in NUDT2, a mRNA decapping and Ap4A hydrolysing enzyme, including novel missense and in-frame deletion variants. We show that these NUDT2 variants lead to a marked loss of enzymatic activity, strongly implicating loss of NUDT2 function as the cause of the disorder. NUDT2-deficient patient fibroblasts exhibit a markedly altered transcriptome, accompanied by changes in mRNA half-life and stability. Amongst the most up-regulated mRNAs in NUDT2-deficient cells, we identified host response and interferon-responsive genes. Importantly, add-back experiments using an Ap4A hydrolase defective in mRNA decapping highlighted loss of NUDT2 decapping as the activity implicated in altered mRNA homeostasis.

Our results confirm that reduction or loss of NUDT2 hydrolase activity is associated with a neurological disease, highlighting the importance of a physiologically balanced mRNA processing machinery for neuronal development and homeostasis.
Baseline Serum and Stool Microbiome Biomarkers Predict Clinical Efficacy and Tissue Molecular Response After Ritlecitinib Induction Therapy in Ulcerative Colitis
Authors: Hassan-Zahraee Mina , Ye Zhan , Xi Li , Dushin Elizabeth , Lee Julie , Romatowski Jacek , Leszczyszyn Jaroslaw , Danese Silvio , Sandborn William J , Banfield Christopher , Gale Jeremy D , Peeva Elena , Longman Randy S , Hyde Craig L , Hung Kenneth E
Published: December 2023

Background and Aims

Ritlecitinib, an oral JAK3/TEC family kinase inhibitor, was well-tolerated and efficacious in the phase 2b VIBRATO study in participants with moderate-to-severe ulcerative colitis [UC]. The aim of this study was to identify baseline serum and microbiome markers that predict subsequent clinical efficacy and to develop noninvasive serum signatures as potential real-time noninvasive surrogates of clinical efficacy after ritlecitinib.

Methods

Tissue and peripheral blood proteomics, transcriptomics, and faecal metagenomics were performed on samples before and after 8 weeks of oral ritlecitinib induction therapy [20 mg, 70 mg, 200 mg, or placebo once daily, N = 39, 41, 33, and 18, respectively]. Linear mixed models were used to identify baseline and longitudinal protein markers associated with efficacy. The combined predictivity of these proteins was evaluated using a logistic model with permuted efficacy data. Differential expression of faecal metagenomics was used to differentiate responders and nonresponders.

Results

Peripheral blood serum proteomics identified four baseline serum markers [LTA, CCL21, HLA-E, MEGF10] predictive of modified clinical remission [MR], endoscopic improvement [EI], histological remission [HR], and integrative score of tissue molecular improvement. In responders, 37 serum proteins significantly changed at Week 8 compared with baseline [false discovery rate of <0.05]; of these, changes in four [IL4R, TNFRSF4, SPINK4, and LAIR-1] predicted concurrent EI and HR responses. Faecal metagenomics analysis revealed baseline and treatment response signatures that correlated with EI, MR, and tissue molecular improvement.

Conclusions

Blood and microbiome biomarkers stratify endoscopic, histological, and tissue molecular responses to ritlecitinib, which may help guide future precision medicine approaches to UC treatment. ClinicalTrials.gov NCT02958865
Sex-limited experimental evolution drives transcriptomic divergence in a hermaphrodite
Authors: Cīrulis Aivars , Nordén Anna K , Churcher Allison M , Ramm Steven A , Zadesenets Kira S , Abbott Jessica K
Published: December 2023

The evolution of gonochorism from hermaphroditism is linked with the formation of sex chromosomes, as well as the evolution of sex-biased and sex-specific gene expression to allow both sexes to reach their fitness optimum. There is evidence that sexual selection drives the evolution of male-biased gene expression in particular. However, previous research in this area in animals comes from either theoretical models or comparative studies of already old sex chromosomes. We therefore investigated changes in gene expression under 3 different selection regimes for the simultaneous hermaphrodite Macrostomum lignano subjected to sex-limited experimental evolution (i.e. selection for fitness via eggs, sperm, or a control regime allowing both). After 21 and 22 generations of selection for male-specific or female-specific fitness, we characterized changes in whole-organism gene expression. We found that female-selected lines had changed the most in their gene expression. Although annotation for this species is limited, gene ontology term and Kyoto Encyclopedia of Genes and Genomes pathway analyses suggest that metabolic changes (e.g. biosynthesis of amino acids and carbon metabolism) are an important adaptive component. As predicted, we found that the expression of genes previously identified as testis-biased candidates tended to be downregulated in the female-selected lines. We did not find any significant expression differences for previously identified candidates of other sex-specific organs, but this may simply reflect that few transcripts have been characterized in this way. In conclusion, our experiment suggests that changes in testis-biased gene expression are important in the early evolution of sex chromosomes and gonochorism.
Hazardous Alcohol Use Among Community-Dwelling Older Adults With Persistent or Recurrent Pain: Findings From the Health and Retirement Study
Authors: LaRowe Lisa R , Miller Angela , Shah Sachin J , Ritchie Christine S
Published: December 2023

Background

Although pain and alcohol use are highly prevalent and associated with deleterious health outcomes among older adults, a paucity of literature has examined hazardous drinking among older adults with pain. We aimed to examine the prevalence of hazardous drinking among a nationally representative sample of older adults with persistent or recurrent pain.

Methods

We conducted cross-sectional analyses of data collected from the 2018 wave of the Health and Retirement Study. Participants included 1  549 community-dwelling adults aged ≥65 with persistent or recurrent pain (ie, clinically significant pain present at 2 consecutive survey waves).

Results

More than one-quarter of older adults with persistent or recurrent pain reported regular alcohol use (≥weekly), nearly half of whom reported hazardous patterns of drinking. Specifically, 32% reported excessive drinking (ie, >2 drinks per day for older men; >1 drink per day for older women), and 22% reported binge drinking (ie, ≥4 drinks on one occasion). Exploratory analyses revealed a high prevalence of hazardous drinking among the subsample of older adults who used opioids (47%).

Conclusions

Hazardous alcohol use—including both excessive and binge drinking—is common among older adults with persistent or recurrent pain, including those who take opioids. Given that hazardous drinking can complicate pain management and increase the risk for adverse opioid effects (eg, overdose), the current findings underscore the importance of assessing and addressing hazardous patterns of alcohol use among older adults with persistent or recurrent pain.
Joint Association of Physical Frailty and Self-Rated Health With Mortality Among Community-Dwelling Older Adults
Authors: Wu Chenkai , Xu Yichen , Tang Junhan , Liu Hua , Xue Qian-Li
Published: December 2023

Background

The relationship between subjective and objective health is complex and not always matched. Although frailty and self-rated health (SRH) have been separately associated with adverse outcomes, their joint effects remained unclear.

Methods

Participants were 5 300 adults ≥60 years from the China Health and Retirement Longitudinal Study in 2011. Frailty, measured by the validated physical frailty phenotype approach, was classified as nonfrail, prefrail, and frail. SRH was categorized into 3 groups: excellent/very good/good, fair, and poor/very poor. We used the Cox models to examine the independent and joint association of frailty and SRH with mortality. We used the interaction approach to determine whether the association of SRH with mortality differed by frailty. Subgroup analyses were conducted by depression and cognitive impairment.

Results

About 8.1% of frail participants reported excellent/very good/good health; 21.2% of the nonfrail reported poor/very poor health. Prefrailty and frailty were associated with a 1.63- and 2.38-fold increase in the hazard of mortality than the nonfrail, respectively, after adjusting for SRH. Reporting fair and poor/very poor health was associated with a 29% and 100% increase in the hazard of mortality, respectively, after adjusting for frailty. No significant interaction was found. Prefrail and frail older adults with excellent/very good/good health had a similar mortality as the nonfrail with poor/very poor SRH. The association of SRH with mortality was less pronounced among individuals with depression or cognitive impairment.

Conclusions

SRH is a potential marker of resilience among people living with frailty that may be a target for ameliorating health risks induced by frailty.
A Frangi filter aided deep learning approach for palaeochannel recognition
Authors: Zhong Ding , Wang Jiaqi , Guo Yixiao , Liu Yicong , Chen Junyang , Xu Tianji
Published: December 2023

In view of the problem of identifying palaeochannels with high concealment and complex geological structures, this paper proposes an intelligent recognition method for palaeochannels based on Frangi filtering and deep learning. The methodology makes use of Maximum Entropy Wigner–Ville Distribution (MEWVD) method to process the original instantaneous amplitude data, which enhance the distinct features of micro palaeochannels in different sensitive frequency bands. The sample 2-D stratigraphic images generated from these data is labelled for the pre-training process of Attention R2U-Net neural network model. Subsequently, Frangi filter is used to identify and enhance the linear structures of river channels in target stratigraphic images, improving the identification effect of the neural network. Finally, RGB data fusion and 3-D visualization carving are performed on the identification data. This method not only eliminates redundant information using the Frangi filter but also proves that the Attention R2U-Net network model structure with attention mechanism and residual convolution structure can effectively improve the segmentation effect for river channels at different scales. Experimental examples show that this method achieves pixel-level feature segmentation of 3-D seismic data for palaeochannels, accurately depicting their shape, width, thickness, flow direction and other features, thus providing support for subsequent well deployment and horizontal well fracturing selection.
Results from the first autologous grafting of adult human testis tissue: a case report
Authors: Jensen Christian Fuglesang S , Mamsen Linn Salto , Wang Danyang , Fode Mikkel , Giwercman Aleksander , Jørgensen Niels , Ohl Dana A , Fedder Jens , Hoffmann Eva R , Yding Andersen Claus , Sønksen Jens
Published: December 2023

Fertility restoration using autologous testicular tissue transplantation is relevant for infertile men surviving from childhood cancer and, possibly, in men with absent or incomplete spermatogenesis resulting in the lack of spermatozoa in the ejaculate (non-obstructive azoospermia, NOA). Currently, testicular tissue from pre-pubertal boys extracted before treatment with gonadotoxic cancer therapy can be cryopreserved with good survival of spermatogonial stem cells. However, strategies for fertility restoration, after successful cancer treatment, are still experimental and no clinical methods have yet been developed. Similarly, no clinically available treatments can help men with NOA to become biological fathers after failed attempts of testicular surgical sperm retrieval. We present a case of a 31-year-old man with NOA who had three pieces of testis tissue (each ∼2 × 4 × 2 mm3) extracted and cryopreserved in relation to performing microdissection testicular sperm extraction (mTESE). Approximately 2 years after mTESE, the thawed tissue pieces were engrafted in surgically created pockets bilaterally under the scrotal skin. Follow-up was performed after 2, 4, and 6 months with assessment of reproductive hormones and ultrasound of the scrotum. After 6 months, all engrafted tissue was extracted and microscopically analyzed for the presence of spermatozoa. Furthermore, parts of the extracted tissue were analyzed histologically and by immunohistochemical analysis. Active blood flow in the engrafted tissue was demonstrated by doppler ultrasound after 6 months. No spermatozoa were found in the extracted tissue. Histological and immunohistochemical analysis demonstrated graft survival with intact clear tubules and normal cell organization. Sertoli cells and spermatocytes with normal morphology were located near the basement membrane. MAGE-A and VASA positive spermatogonia/spermatocytes were detected together with SOX9 positive Sertoli cells. Spermatocytes and/or Sertoli cells positive for γH2AX was also detected. In summary, following autologous grafting of frozen-thawed testis tissue under the scrotal skin in a man with NOA, we demonstrated graft survival after 6 months. No mature spermatozoa were detected; however, this is likely due to the pre-existing spermatogenic failure.
Accuracy, acceptability and feasibility of photography for use in trachoma surveys: a mixed methods study in Tanzania
Authors: Bisanzio Donal , Butcher Robert , Turbé Valérian , Matsumoto Kenji , Dinesh Chaitra , Massae Patrick , Dejene Michael , Jimenez Cristina , Macleod Colin , Matayan Einoti , Mpyet Caleb , Pavluck Alex , Saboyá-Díaz Martha Idalí , Tadesse Fentahun , Talero Sandra Liliana , Solomon Anthony W , Ngondi Jeremiah , Kabona George , Uisso Cecilia , Simon Alistidia , Mwingira Upendo , Harding-Esch Emma M
Published: December 2023

Background

Photography could be used to train individuals to diagnose trachomatous inflammation—follicular (TF) as trachoma prevalence decreases and to ensure accurate field TF grading in trachoma prevalence surveys. We compared photograph and field TF grading and determined the acceptability and feasibility of eyelid photography to community members and trachoma survey trainers.

Methods

A total of 100 children ages 1–9 y were examined for TF in two Maasai villages in Tanzania. Two images of the right everted superior tarsal conjunctiva of each child were taken with a smartphone and a digital single-lens reflex (DSLR) camera. Two graders independently graded all photos. Focus group discussions (FGDs) were conducted with community members and Tropical Data trainers.

Results

Of 391 photos, one-fifth were discarded as ungradable. Compared with field grading, photo grading consistently underdiagnosed TF. Compared with field grading, DSLR photo grading resulted in a higher prevalence and sensitivity than smartphone photo grading. FGDs indicated that communities and trainers found photography acceptable and preferred smartphones to DSLR in terms of practicalities, but image quality was of paramount importance for trainers.

Conclusions

Photography is acceptable and feasible, but further work is needed to ensure high-quality images that enable accurate and consistent grading before being routinely implemented in trachoma surveys.
Effects of a team Quality Improvement method in a national clinical audit programme of four clinical specialties in Ministry of Health hospitals in Saudi Arabia
Authors: Alghamdi Saleh , Dixon Nancy , Al-Senani Fahmi , Al Aseri Zohair , Al Saif Shukri , AlTahan Talal
Published: December 2023

In 2018, the Ministry of Health (MoH) in Saudi Arabia developed a clinical excellence strategy. An objective was to reduce variation in clinical practices in MoH hospitals, particularly for conditions with high mortality in Saudi Arabia, by applying best practice clinical standards and using the clinical audit process to measure clinical practice. The strategy included working with multiprofessional teams in hospitals to implement improvements needed in clinical practice. To test the feasibility of carrying out national clinical audits in MoH hospitals, audits were carried out in 16 MoH hospitals on four clinical subjects—acute myocardial infarction, major trauma, sepsis, and stroke. Clinical expert groups, including Saudi clinicians and an international clinical expert, developed clinical care standards for the four conditions from analyses of international and Saudi clinical guidelines. The audits were designed with the expert groups. Multiprofessional teams were appointed to carry out the audits in designated MoH hospitals. Data collectors in each hospital were trained to collect data. Workshops were held with the teams on the clinical care standards and how data would be collected for the audits, and later, on the findings of data collection and how to use the improvement process to implement changes to improve compliance with the standards. After 4 months, data collection was repeated to determine if compliance with the clinical care standards had improved. Data collected from each hospital for both cycles of data collection were independently reliably tested. All designated hospitals participated in the audits, collecting and submitting data for two rounds of data collection and implementing improvement plans after the first round of data collection. All hospitals made substantial improvements in clinical practices. Of a total of 84 measures used to assess compliance with a total of 52 clinical care standards for the four clinical conditions, improvements were made by hospital teams in 58 (69.1%) measures. Improvements were statistically significant for 34 (40.5%) measures. The project demonstrated that well-designed and executed audits using evidence-based clinical care standards can result in substantial improvements in clinical practices in MoH hospitals in Saudi Arabia. Keys to success were the improvement methodology built into the audit process and the requirement for hospitals to appoint multiprofessional teams to carry out the audits. The approach adds to evidence on the effectiveness of clinical audits in achieving improvements in clinical quality and can be replicated in national audit programmes.
What If We Were There? A Counter-Factual Call for IR to Engage with Material-Technological Making
Authors: Austin Jonathan Luke , Leander Anna
Published: December 2023

International relations (IR) shows growing interest in expanding its practical engagements into different domains: the visual, the artistic, the aesthetic, the diagrammatic, and so forth. But a gap remains. Despite widespread acknowledgment of the political transformations caused by material and technological change across world politics, IR rarely fully integrates forms of material-technological praxis into its work. We rarely make digital, architectural, computational, or other seemingly technical things within IR. This article suggests we should start doing so, in direct collaboration with practitioners, applied scientists, and technical experts. Specifically, it suggests that engaging in material-technological making has the potential to (1) increase our basic scientific knowledge of politics, (2) augment our capacity to theorize politics, and (3) radically expand how we normatively and political intervene in politics. To make that argument, the paper conducts a speculative form of counter-factual analysis of the kind of “difference” that might have been made if scholars of IR had been involved in the development of three technologies designed by the International Committee of the Red Cross for humanitarian purposes. In doing so, we show that the exclusion of the material-technological from IR’s praxis is not only damaging to its vitality as an intellectual field, but also an abdication of what Haraway terms its ethico-political response-ability within politics.
From illness management to quality of life: rethinking consumer health informatics opportunities for progressive, potentially fatal illnesses
Authors: Antonio Marcy G , Veinot Tiffany C
Published: December 2023

Objectives

Investigate how people with chronic obstructive pulmonary disease (COPD)—an example of a progressive, potentially fatal illness—are using digital technologies (DTs) to address illness experiences, outcomes and social connectedness.

Materials and Methods

A transformative mixed methods study was conducted in Canada with people with COPD (n = 77) or with a progressive lung condition (n = 6). Stage-1 interviews (n = 7) informed the stage-2 survey. Survey responses (n = 80) facilitated the identification of participants for stage-3 interviews (n = 13). The interviews were thematically analyzed. Descriptive statistics were calculated for the survey. The integrative mixed method analysis involved mixing between and across the stages.

Results

Most COPD participants (87.0%) used DTs. However, few participants frequently used DTs to self-manage COPD. People used DTs to seek online information about COPD symptoms and treatments, but lacked tailored information about illness progression. Few expressed interest in using DTs for self- monitoring and tracking. The regular use of DTs for intergenerational connections may facilitate leaving a legacy and passing on traditions and memories. Use of DTs for leisure activities provided opportunities for connecting socially and for respite, reminiscing, distraction and spontaneity.

Discussion and Conclusion

We advocate reconceptualizing consumer health technologies to prioritize quality of life for people with a progressive, potentially fatal illness. “Quality of life informatics” should focus on reducing stigma regarding illness and disability and taboo towards death, improving access to palliative care resources and encouraging experiences to support social, emotional and mental health. For DTs to support people with fatal, progressive illnesses, we must expand informatics strategies to quality of life.
Engineered biosynthesis of plant heteroyohimbine and corynantheine alkaloids in Saccharomyces cerevisiae
Authors: Dror Moriel J , Misa Joshua , Yee Danielle A , Chu Angela M , Yu Rachel K , Chan Bradley B , Aoyama Lauren S , Chaparala Anjali P , O'Connor Sarah E , Tang Yi
Published: December 2023

Monoterpene indole alkaloids (MIAs) are a class of natural products comprised of thousands of structurally unique bioactive compounds with significant therapeutic values. Due to difficulties associated with isolation from native plant species and organic synthesis of these structurally complex molecules, microbial production of MIAs using engineered hosts are highly desired. In this work, we report the engineering of fully integrated Saccharomyces cerevisiae strains that allow de novo access to strictosidine, the universal precursor to thousands of MIAs at 30–40 mg/L. The optimization efforts were based on a previously reported yeast strain that is engineered to produce high titers of the monoterpene precursor geraniol through compartmentalization of mevalonate pathway in the mitochondria. Our approaches here included the use of CRISPR-dCas9 interference to identify mitochondria diphosphate transporters that negatively impact the titer of the monoterpene, followed by genetic inactivation; the overexpression of transcriptional regulators that increase cellular respiration and mitochondria biogenesis. Strain construction included the strategic integration of genes encoding both MIA biosynthetic and accessory enzymes into the genome under a variety of constitutive and inducible promoters. Following successful de novo production of strictosidine, complex alkaloids belonging to heteroyohimbine and corynantheine families were reconstituted in the host with introduction of additional downstream enzymes. We demonstrate that the serpentine/alstonine pair can be produced at ∼5 mg/L titer, while corynantheidine, the precursor to mitragynine can be produced at ∼1 mg/L titer. Feeding of halogenated tryptamine led to the biosynthesis of analogs of alkaloids in both families. Collectively, our yeast strain represents an excellent starting point to further engineer biosynthetic bottlenecks in this pathway and to access additional MIAs and analogs through microbial fermentation.

One Sentence Summary

An Saccharomyces cerevisiae-based microbial platform was developed for the biosynthesis of monoterpene indole alkaloids, including the universal precursor strictosidine and further modified heteroyohimbine and corynantheidine alkaloids.
Gendered ecologies: Explaining interprofessional and gender inequalities in Ontario midwifery
Authors: Siberry Alexandra V , Adams Tracey L
Published: December 2023

Although midwifery has been a self-regulating profession in Ontario, Canada for over 30 years, practitioners continue to face barriers and inequalities due to the intersection of professional and gender dynamics. To understand these dynamics better we develop a gendered ecologies approach, refining ecological theories of professions by drawing on research on gender and professions. We then apply this approach when analysing qualitative in-depth interviews with a sample of Ontario midwives about their work. We argue that a gendered ecological approach—by underscoring that gender and professional inequalities are reproduced at the micro, meso, and macro levels by gendered actors contesting (gendered) spaces as they pursue a variety of interests—illuminates midwives’ struggles on the job and their continued subordination within the Ontario healthcare system.
Emissions intensity: do we need a CBAM for oil and gas imports?
Authors: Hilson Chris
Published: December 2023

The UK has seen significant recent attention being paid to the issue of the ‘emissions intensity’ of oil and gas operations, with the oil and gas industry and the Government using this as a climate justification for domestic North Sea production over imported oil and gas. This commentary explores these arguments in the context of the Rosebank decision and examines why emission intensity matters for lawyers. One key reason identified involves trade: without a carbon border adjustment mechanism (tax) or equivalent on imports of oil and gas from countries with poor records on electrification, flaring and vented emissions, domestic oil and gas production faces unfair climate competition.
Strong 21-cm fluctuations and anisotropy due to the line-of-sight effect of radio galaxies at cosmic dawn
Authors: Sikder Sudipta , Barkana Rennan , Fialkov Anastasia , Reis Itamar
Published: December 2023

The reported detection of the global 21-cm signal by the EDGES collaboration is significantly stronger than standard astrophysical predictions. One possible explanation is an early radio excess above the cosmic microwave background. Such a radio background could have been produced by high-redshift galaxies, if they were especially efficient in producing low-frequency synchrotron radiation. We have previously studied the effects of such an inhomogeneous radio background on the 21-cm signal; however, we made a simplifying assumption of isotropy of the background seen by each hydrogen cloud. Here, we perform a complete calculation that accounts for the fact that the 21-cm absorption occurs along the line of sight, and is therefore sensitive to radio sources lying behind each absorbing cloud. We find that the complete calculation strongly enhances the 21-cm power spectrum during cosmic dawn, by up to two orders of magnitude; on the other hand, the effect on the global 21-cm signal is only at the 5 per cent level. In addition to making the high-redshift 21-cm fluctuations potentially more easily observable, the line-of-sight radio effect induces a new anisotropy in the 21-cm power spectrum. While these effects are particularly large for the case of an extremely enhanced radio efficiency, they make it more feasible to detect even a moderately enhanced radio efficiency in early galaxies. This is especially relevant since the EDGES signal has been contested by the SARAS experiment.
Laboratory astrochemical investigation of H-atom reactions and photochemistry of [H, C, N, S] isomers: astrophysical significance and implications
Authors: Keresztes Barbara , Góbi Sándor , Tarczay György
Published: December 2023

The astrochemically relevant reactions of [H, C, N, S] isomers were studied both theoretically and experimentally. The energetics and barriers of H-atom-addition and H-atom-abstraction reactions were computed. Experimentally, [H, C, N, S] isomers were generated via in situ photolysis in a solid para-H2 matrix. The H-atom reaction and the photochemistry of these species were monitored by infrared spectroscopy. In the case of HNCS, the formation of HNCSH was observed. Tentatively two different conformers, syn,trans- and anti,trans-HNCSH, were identified. The subsequent H-atom-addition and H-atom-abstraction reactions did not effectively induce the isomerization of HNCS to HSCN. In the case of HCNS, the observation of the HCN product indirectly reveals H-atom addition to the S atom of HCNS, which is followed by the rupture of the N−S bond. While not explored experimentally, theoretical computations reveal negligible barrier heights for the H-atom-abstraction reactions of HSCN and HSNC. Therefore, H atoms might deplete these species in the interstellar medium (ISM). In contrast to the H-atom reactions, ultraviolet (UV) irradiation between 255 and 240 nm effectively isomerized the HNCS to HSCN and HSNC. Besides decomposition, HCNS isomerize to HNCS, HSCN, and HSNC upon exposure to UV radiation between 300 and 216 nm. In certain H-atom-free conditions, HSNC, not yet observed in the ISM, could potentially coexist in observable amounts with the already detected HNCS and HSCN in the ISM. Conversely, HCNS, another unidentified isomer in the ISM, is unlikely to accumulate there under UV radiation or in the presence of reactive radicals, including H atoms.
Critical magnetic Reynolds number of the turbulent dynamo in collisionless plasmas
Authors: Achikanath Chirakkara Radhika , Seta Amit , Federrath Christoph , Kunz Matthew W
Published: December 2023

The intracluster medium of galaxy clusters is an extremely hot and diffuse, nearly collisionless plasma, which hosts dynamically important magnetic fields of ∼μG strength. Seed magnetic fields of much weaker strength of astrophysical or primordial origin can be present in the intracluster medium. In collisional plasmas, which can be approximated in the magnetohydrodynamical (MHD) limit, the turbulent dynamo mechanism can amplify weak seed fields to strong dynamical levels efficiently by converting turbulent kinetic energy into magnetic energy. However, the viability of this mechanism in weakly collisional or completely collisionless plasma is much less understood. In this study, we explore the properties of the collisionless turbulent dynamo using three-dimensional hybrid-kinetic particle-in-cell simulations. We explore the properties of the collisionless turbulent dynamo in the kinematic regime for different values of the magnetic Reynolds number, Rm, initial magnetic-to-kinetic energy ratio, (Emag/Ekin)i, and initial Larmor ratio, (rLarmor/Lbox)i, i.e. the ratio of the Larmor radius to the size of the turbulent system. We find that in the ‘un-magnetized’ regime, (rLarmor/Lbox)i > 1, the critical magnetic Reynolds number for the dynamo action Rmcrit ≈ 107 ± 3. In the ‘magnetized’ regime, (rLarmor/Lbox)i ≲ 1, we find a marginally higher Rmcrit = 124 ± 8. We find that the growth rate of the magnetic energy does not depend on the strength of the seed magnetic field when the initial magnetization is fixed. We also study the distribution and evolution of the pressure anisotropy in the collisionless plasma and compare our results with the MHD turbulent dynamo.
Regional variation in incidence and prognosis of acute kidney injury
Authors: Jensen Simon Kok , Rasmussen Thomas Bøjer , Jacobsen Bjarke Hejlskov , Heide-Jørgensen Uffe , Sawhney Simon , Gammelager Henrik , Birn Henrik , Johnsen Søren Paaske , Christiansen Christian Fynbo
Published: December 2023

Background

Examining regional variation in acute kidney injury (AKI) and associated outcomes may reveal inequalities and possibilities for optimization of the quality of care. Using the Danish medical databases, we examined regional variation in the incidence, follow-up and prognosis of AKI in Denmark.

Methods

Patients with one or more AKI episodes in 2017 were identified using population-based creatinine measurements covering all Danish residents. Crude and sex-and-age-standardized incidence rates of AKI were estimated using census statistics for each municipality. Adjusted hazard ratios (aHR) of chronic kidney disease (CKD), all-cause death, biochemical follow-up and outpatient contact with a nephrology department after AKI were estimated across geographical regions and categories of municipalities, accounting for differences in demographics, comorbidities, medication use, lifestyle and social factors, and baseline kidney function.

Results

We identified 63 382 AKI episodes in 58 356 adults in 2017. The regional standardized AKI incidence rates ranged from 12.9 to 14.9 per 1000 person-years. Compared with the Capital Region of Denmark, the aHRs across regions ranged from 1.04 to 1.25 for CKD, from 0.97 to 1.04 for all-cause death, from 1.09 to 1.15 for biochemical follow-up and from 1.08 to 1.49 for outpatient contact with a nephrology department after AKI. Similar variations were found across municipality categories.

Conclusions

Within the uniform Danish healthcare system, we found modest regional variation in AKI incidence. The mortality after AKI was similar; however, CKD, biochemical follow-up and nephrology follow-up after AKI varied across regions and municipality categories.
Systemic Risk and Monetary Policy: The Haircut Gap Channel of the Lender of Last Resort
Authors: Jasova Martina , Laeven Luc , Mendicino Caterina , Peydró José-Luis , Supera Dominik
Published: December 2023

We show that lender of last resort (LOLR) policy exacerbates bank interconnectedness. Using novel micro-level data, we analyze LOLR’s haircut gaps: the differences between the private market and central bank haircuts. LOLR policy incentivizes banks to increase pledging and holdings of higher haircut-gap bonds, especially those issued by domestic and systemically important banks. Effects only apply to banks, not to nonbanks without LOLR access. LOLR funding revives bank bond issuance associated with higher haircut gaps and increases the subsequent correlation between pledging and issuing banks’ bond prices, in particular during periods of low-market returns and for domestic, systemically important banks.
The incidence and prevalence of juvenile idiopathic arthritis differs between ethnic groups in England
Authors: Beesley Richard P , Hyrich Kimme L , Humphreys Jenny H
Published: December 2023

Objectives

JIA is a heterogeneous group of rare autoimmune disorders characterized by chronic joint inflammation of unknown aetiology with onset under 16 years. Accurate estimates of disease rates help understand impacts on individuals and society, and provide evidence for health service planning and delivery. This study aimed to produce the first national estimates of incidence and prevalence by ethnic group using electronic health records.

Methods

Data from the Clinical Practice Research Datalink Aurum, a primary care electronic health record database in England, were used to estimate the incidence and prevalence of JIA by ethnic group amongst children and young people aged under 16 years between 2003 and 2018, with cases validated using Hospital Episode Statistics. χ2 was used to test the difference in proportions compared with the ethnic distribution of England.

Results

A total of 424 incident cases of JIA were identified, 389 validated using Hospital Episode Statistics records. Incidence of JIA was higher amongst those of white ethnic group (6.2 per 100 000 population) compared with mixed (3.0 per 100 000), Asian (2.7 per 100 000) and Black (2.9 per 100 000) communities. The ethnic group distribution of cases differed significantly compared with the general population (P < 0.0001).

Conclusion

The incidence and prevalence of JIA differs between ethnic groups, and is different from the general population. This is likely to be due to a combination of genetic and equity factors. Further research to understand the underlying cause of these differences is important to enable targeted interventions and appropriate service provision.
Protective impacts of Artemisia annua against hepatic toxicity induced by gentamicin
Authors: Althobaiti Saed A , Qahl Safa H , Toufig Hind , Almalki Daklallah A , Nasir Omaima , Soliman Mohamed Mohamed
Published: December 2023

The current study aimed to investigate the ameliorative effects of Artemisia annua (RA) extract on hepatic toxicity induced by gentamicin injection mice. Sixteen mice were divided into four groups; the control group received saline, the second group received 1% A. annua (RA) extract, third group injected 80 mg/kg gentamicin (GEN) intraperitoneally. The protective group treated with a combination of GEN and A. annua. All mice were treated for consecutive 15 days. Results confirmed that hepatic biomarkers (GPT, GCT, GOT, IL-6 and IL-1β), all were altered after gentamycin injection. The histological analysis confirmed that gentamycin injected mice showed portal vein congestion, micro and macro steatosis, and nuclear pyknosis of hepatocytes. The protective group showed intact central vein with less microsteatosis of some hepatocytes. Immunochemistry analysis confirmed that the immunoreactivity of COX-2 gene showed negative impact in examined groups. Unlike, NF-κB gene exhibited diffuse positive expression in the gentamicin group. TGF-β1 immunoreactivity was mild positive in control and highly upregulated in gentamicin treated mice, all were normalized after RA administration. In conclusion, RA showed a beneficial impact against gentamycin induced hepatic toxicity at cellular and biochemical levels by regulating proteins and inflammatory markers associated with liver activity.
A systematic review of the Iberian springsnail subgenus Alzoniella (Navarriella) (Caenogastropoda: Hydrobiidae), with the description of a new potentially relict subfamily
Authors: García-Guerrero Fernando , Miller Jonathan P , Delicado Diana , Novo Marta , Ramos Marian A
Published: December 2023

The threatened springsnail subgenus Alzoniella (Navarriella) in the Iberian Peninsula has been suggested to be an old and relict lineage of the family Hydrobiidae. The subgenus is represented by two morphological species, both endemic to the Pyrenees and their southern foothills. We conducted phylogenetic analyses based on mitochondrial and nuclear gene fragments of topotypes and other populations, four molecular species delimitation methods, and morphological examinations to clarify the uncertain systematic position of the subgenus within the family, assess its species diversity, and understand the population genetic structure of the two geographically restricted species. Our phylogenetic results revealed that Alzoniella (Navarriella) is distantly related to all other species of Alzoniella, even belonging to an independent subfamily-level clade, for which we introduce the new genus Navarriella and the new subfamily Navarriellinae subfam. nov. Molecular methods and geometric morphometric analysis of shell shape identified a single species in the new genus. The significant phylogenetic distance from other hydrobiid taxa, narrow distribution, and limited gene flow among its populations (estimated from mitochondrial cytochrome c oxidase subunit I sequences) highlight Navarriella as an isolated lineage within the family that requires urgent conservation attention. Furthermore, our results cast a new light on the northern Iberian Mountains as a dispersal barrier for ancient spring lineages.
Into the Unknown: Navigating a Path as an Early-stage Physician-scientist in Obstetrics and Gynecology
Authors: Wernimont Sarah A.
Published: December 2023

This piece is a reflection of one early-stage physician-scientist’s professional journey. It highlights a few challenges of navigating this path while calling for continued investment and support for physician-scientists to enhance maternal and child lifelong health.
Decreases in Employer Referrals to First-Time Substance Use Treatment for Adults From 2004 to 2020
Authors: Ware Orrin D. , Hussong Andrea , Frey Jodi J. , Daughters Stacey , Cloeren Marianne , Gryczynski Jan , Lister Jamey J. , Jordan Robyn
Published: December 2023

Objective

The aim of the study is to examine trends of employer/employee assistance program referred admissions to outpatient substance use disorder (SUD) treatment in the United States.

Methods

The publicly available Treatment Episode Data Set was used. Full-time employed adults with no history of SUD treatment referred to outpatient treatment by an employer/employee assistance program from 2004 to 2020 were included (N = 36,142). Joinpoint regression examined admission trends.

Results

Employer/employee assistance program referred admissions to outpatient treatment decreased annually by 6.4% from 2004 to 2020 (P < 0.001). Joinpoint analyses identified 2 linear segments from 2004 to 2008 (increased but not significant) and from 2008 to 2020. From 2008 to 2020, an average annual percent decrease of 8.7% (P < 0.001) was identified.

Conclusions

Findings from this repeated cross-sectional study suggest a missed opportunity for workplaces to serve as a potential SUD treatment access point.
Pericardial Closure With Expanded Polytetrafluoroethylene Patch in Left Ventricular Assist Device Surgery
Authors: Meinert Étienne F. R. C. , Kremer Jamila , Tochtermann Ursula , Sommer Wiebke , Warnecke Gregor , Karck Matthias , Meyer Anna L.
Published: December 2023

To reduce adhesions after left ventricular assist device (LVAD) implantation, pericardial closure using an expanded polytetrafluoroethylene (ePTFE) patch has been suggested. However, as foreign material, ePTFE patches could increase the risk of infectious complications. In this single-center retrospective study, we investigated outcomes of pericardial closure using an ePTFE patch in LVAD implantation. We included all patients who underwent LVAD implantation at our center between 2011 and 2020 (n = 166). Primary endpoint was development of mediastinitis at any point of time between LVAD implantation and heart transplantation (HTx) or death. Secondary endpoint was overall survival. Preoperative and postoperative clinical data were collected to ensure comparability between the groups. We included 166 patients with LVAD. A total of 116 patients (70%) underwent pericardial closure using an ePTFE patch. There were significant differences between the groups in treatment setting, previous cardiac surgery, Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) level, development of driveline infection, and HTx. Patients with an ePTFE patch developed mediastinitis more frequently (16%) than patients without ePTFE patch (4%) (p = 0.039). A significant difference in overall survival between the groups could not be confirmed (p = 0.29). The use of PTFE patches for pericardial closure in LVAD implantation was associated with a higher incidence of mediastinitis, but not with a difference in overall survival.
The science of joy: happiness among healthcare workers
Authors: Caraballo-Arias Yohama , Feola Daniela , Milani Simona
Published: December 2023

Purpose of review

Understanding the impact of healthcare workers’ (HCW) happiness on patient care is crucial.

The aim of this review is to provide an update on recent advances in the field.

Recent findings

The article depicts the importance of HCW's happiness; the factors, the psychometric tests, tools and methods to measure their happiness and wellbeing, as well as interventions that organizations can implement to improve it, summarizing what have been published from January 2022 up to August 2023.

HCW often face demanding work environments, long working hours, and emotional challenges when dealing with patients’ suffering. The constant exposure to such stressors can lead to physical and mental health issues. Factors like job satisfaction, work-life balance, and support from colleagues and supervisors play a significant role in their happiness. Tools such as the Shorted Happiness at Work Scale (SHAW) and Eudemonic and Hedonic happiness investigation, and other surveys and qualitative methods have been used to assess overall well being. Organizational strategies have been implemented to promote a positive work culture, recognize and reward efforts, and create a supportive environment to improve happiness. Mindfulness-based techniques, web-based interventions, practice gratitude, peer support programs, and stress management training seem to be effective measures to enhance the wellbeing of HCW.
Altered defense patterns upon retrotransposition highlights the potential for rapid adaptation by transposable elements
Authors: Aller Emma S.T. , Kanstrup Christa , Hunziker Pascal , Kliebenstein Daniel J. , Burow Meike
Published: December 2023

Transposable elements can be activated in response to environmental changes and lead to changes in DNA sequence. Their target sites of insertions have previously been thought to be random, but this theory has lately been contradicted. For instance, mobilization is favored towards genes involved in regulatory processes. This makes them interesting as potential players in rapid responses required under stressful environmental conditions. In this paper, we report the in-depth characterization of anArabidopsis thalianaCol-0-based line whose altered DNA methylation pattern made it vulnerable for transposable element movement. We identified a transposable element retrotransposition into a transporter of glucosinolate defense compounds. As a consequence of this transposable element movement, the plants showed tissue-specific changes in glucosinolate profiles and levels accompanied by rewiring of glucosinolate- and defense-related transcriptional changes. As this single transposable element had strong impact on the plants’ resistance to insect herbivory, our findings highlight the potential for transposable elements to play a role in plant adaptation.