bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the Clinical Utility of a Long-Read Sequencing-Based Approach in Prenatal Diagnosis of Thalassemia
Authors: Liang Qiaowei , He Jun , Li Qing , Zhou Yulin , Liu Yanqiu , Li Youqiong , Tang Lingfang , Huang Shengwen , Li Rong , Zeng Fanqian , Mao Aiping , Liu Yinyin , Liang Desheng , Wu Lingqian
Published: January 2023

Background

The aim is to evaluate the clinical utility of a long-read sequencing-based approach termed comprehensive analysis of thalassemia alleles (CATSA) in prenatal diagnosis of thalassemia.

Methods

A total of 278 fetuses from at-risk pregnancies identified in thalassemia carrier screening by PCR-based methods were recruited from 9 hospitals, and PCR-based methods were employed for prenatal diagnosis. CATSA was performed retrospectively and blindly for all 278 fetuses.

Results

Among the 278 fetuses, 263 (94.6%) had concordant results and 15 (5.4%) had discordant results between the 2 methods. Of the 15 fetuses, 4 had discordant thalassemia variants within the PCR detection range and 11 had additional variants identified by CATSA. Independent PCR and Sanger sequencing confirmed the CATSA results. In total, CATSA and PCR-based methods correctly detected 206 and 191 fetuses with variants, respectively. Thus, CATSA yielded a 7.9% (15 of 191) increment as compared with PCR-based methods. CATSA also corrected the predicted phenotype in 8 fetuses. Specifically, a PCR-based method showed one fetus had homozygous HBB c.52A > T variants, while CATSA determined the variant was heterozygous, which corrected the predicted phenotype from β-thalassemia major to trait, potentially impacting the pregnancy outcome. CATSA additionally identified α-globin triplicates in 2 fetuses with the heterozygous HBB c.316-197C > T variant, which corrected the predicted phenotype from β-thalassemia trait to intermedia and changed the disease prognosis.

Conclusions

CATSA represents a more comprehensive and accurate approach that potentially enables more informed genetic counseling and improved clinical outcomes compared to PCR-based methods.
Irreducible Fuzzy Multiset Finite Automaton
Authors: Shamsizadeh Marzieh , Mehdi Zahedi Mohammad , Abolpour Khadijeh
Published: January 2023

This study aims to investigate the algebraic properties of fuzzy multiset finite automaton (FMFA), giving a congruence relation. Using the equivalence classes, a minimal accessible complete FMFA is then presented. In addition, we define the concepts of admissible relation, admissible partition for FMFA and quotient FMFA. Further, we present an algorithm which determines an admissible partition for an FMFA and we suggest the time complexity of the algorithm. In particular, we introduce a connection between the admissible partition and the quotient FMFA and we show that any quotient of a given FMFA and the FMFA itself have the same language. Furthermore, using the quotient FMFA, we obtain an irreducible FMFA with the same language.
Improved (Related-Key) Differential-Based Neural Distinguishers for SIMON and SIMECK Block Ciphers
Authors: Lu Jinyu , Liu Guoqiang , Sun Bing , Li Chao , Liu Li
Published: January 2023

In CRYPTO 2019, Gohr made a pioneering attempt and successfully applied deep learning to the differential cryptanalysis against NSA block cipher Speck 32/64, achieving higher accuracy than the pure differential distinguishers. By its very nature, mining effective features in data plays a crucial role in data-driven deep learning. In this paper, in addition to considering the integrity of the information from the training data of the ciphertext pair, domain knowledge about the structure of differential cryptanalysis is also considered into the training process of deep learning to improve the performance. Meanwhile, taking the performance of the differential-neural distinguisher of Simon 32/64 as an entry point, we investigate the impact of input difference on the performance of the hybrid distinguishers to choose the proper input difference. Eventually, we improve the accuracy of the neural distinguishers of Simon 32/64, Simon 64/128, Simeck 32/64 and Simeck 64/128. We also obtain related-key differential-based neural distinguishers on round-reduced versions of Simon 32/64, Simon 64/128, Simeck 32/64 and Simeck 64/128 for the first time.
Can scale cortisol concentration be quantified non-lethally in wild fish species?
Authors: Kennedy Emily K C , Janz David M
Published: January 2023

Cortisol, the primary glucocorticoid in fishes, is secreted into the bloodstream in response to stress. Circulating cortisol accumulates in scales, a durable calcified structure that can be easily sampled from many fish species. As such, the use of scale cortisol concentration (SCC) is currently being explored as a means of chronic stress biomonitoring in wild fishes. Scales serve an important role in fish physiology and thus the number of scales required for reliable cortisol analysis is a limiting factor in the non-lethal collection of such samples. To date, scale cortisol quantification has also only been performed non-lethally in captive fishes and due to differences in stress responsiveness SCCs likely differ in wild species. As such, this study aimed to (1) apply our fish scale processing and analysis protocol to wild fish species and (2) apply it to five north temperate fish species to provide information useful to future non-lethal scale sampling regimes. Cortisol was successfully measured in scales collected from wild northern pike (Esox lucius), walleye (Sander vitreus), whitefish (Coregonus clupeaformis), white sucker (Catostomus commersonii) and captive rainbow trout (Oncorhynchus mykiss). SCCs were significantly different between species and thus the sample mass required for reliable cortisol analysis differed as well. In addition to the size of the fish and the mass of their scales this is an important consideration for future scale cortisol analyses as these factors could make SCC an attainable non-lethal sample matrix in some species of fish but impractical in others.
Serum N-Glycomic Biomarkers Predict Treatment Escalation in Inflammatory Bowel Disease
Authors: Shubhakar Archana , Jansen Bas C , Adams Alex T , Reiding Karli R , Ventham Nicholas T , Kalla Rahul , Bergemalm Daniel , Urbanowicz Paulina A , Gardner Richard A ,   IBD-BIOM Consortium, Wuhrer Manfred , Wuhrer Manfred , Halfvarson Jonas , Satsangi Jack , Fernandes Daryl L , Spencer Daniel I R
Published: January 2023

Biomarkers to guide clinical decision making at diagnosis of inflammatory bowel disease [IBD] are urgently needed. We investigated a composite serum N-glycomic biomarker to predict future disease course in a discovery cohort of 244 newly diagnosed IBD patients. In all, 47 individual glycan peaks were analysed using ultra-high performance liquid chromatography, identifying 105 glycoforms from which 24 derived glycan traits were calculated. Multivariable logistic regression was performed to determine associations of derived glycan traits with disease. Cox proportional hazard models were used to predict treatment escalation from first-line treatment to biologics or surgery (hazard ratio [HR] 25.9, p = 1.1 × 10-12; 95% confidence interval [CI], 8.52–78.78). Application to an independent replication cohort of 54 IBD patients yielded an HR of 5.1 [p = 1.1 × 10-5; 95% CI, 2.54–10.1]. These data demonstrate the prognostic capacity of serum N-glycan biomarkers and represent a step towards personalised medicine in IBD.
Racial and Ethnic Trajectories of Sleep Disturbances: Variations by Age and Cohort
Authors: Chen Jen-Hao
Published: January 2023

Background

The racial and ethnic differences in trajectories of sleep disturbances in later life are crucial for addressing health disparities, but are not well understood. This study examines (a) how trajectories of sleep disturbances vary by race and ethnicity and birth cohort and (b) whether social and health risk factors explain such variations.

Methods

The study uses longitudinal data from the 2002–2018 Health and Retirement Study (N = 21 963) and the multilevel growth curve model to assess trajectories of sleep disturbances and their variations across 6 cohorts of White, Black, and Hispanic older adults. Sleep disturbances are measured using a modified Jenkins Sleep Scale.

Results

Without controls, sleep disturbances increased with aging for all racial and ethnic groups, but more rapidly among minorities, particularly younger cohorts of Hispanic older adults. When controlling for social and health risks, sleep disturbances did not change with aging for Whites and Blacks and increased for younger cohorts of Hispanics. Cohort effects were observed among White older adults, with higher sleep disturbances in younger cohorts. Importantly, the racial and ethnic disparities in age and cohort effects were not fully explained by social and health risks. Of the symptoms, the most salient racial and ethnic disparities were found in “waking up at night” and “not feeling rested.”

Conclusions

Findings reveal several differences by race and ethnicity and birth cohort in trajectories of sleep disturbances. Efforts should be made to improve sleep health for older adults as they age, especially for younger cohorts of Blacks and Hispanics.
Fundamental Invariants of Tensors, Latin Hypercubes, and Rectangular Kronecker Coefficients
Authors: Amanov Alimzhan , Yeliussizov Damir
Published: January 2023

We study polynomial SL-invariants of tensors, mainly focusing on fundamental invariants that are of smallest degrees. In particular, we prove that certain 3-dimensional analogue of the Alon–Tarsi conjecture on Latin cubes considered previously by Bürgisser and Ikenmeyer implies positivity of (generalized) Kronecker coefficients at rectangular partitions and as a result provides values for degree sequences of fundamental invariants.
B cell-intrinsic DNase1L3 is essential for the T cell-independent type II response in mice
Authors: Kato Kei , Haniuda Kei , Fukao Saori , Kitamura Daisuke
Published: January 2023

T cell independent type II (TI-II) antigens, such as capsular polysaccharides, have multivalent epitopes, which induce B cell activation, plasma cell differentiation and antibody production by strongly cross-linking B cell receptors. However, the mechanism of B cell activation by TI-II antigens remains unclear. In this study, we demonstrate that DNA endonuclease DNase1L3 (also termed DNase γ) is required for the TI-II response. The production of antigen-specific antibodies was severely diminished in DNase1L3-deficient mice upon immunization with TI-II antigens, but not with T cell dependent (TD) antigens. Bone marrow chimeric mice and B cell transfer experiments revealed that B cell-intrinsic DNase1L3 was required for the TI-II response. DNase1L3-deficient B cells were defective in cell proliferation and plasma cell differentiation in the TI-II response in vivo as well as in vitro, which was not rescued by co-culture with DNase1L3-sufficient B cells in vitro, disproving an involvement of a secretory DNase1L3. In vitro stimulation with TI-II antigen transiently increased expression of DNase1L3 and its translocation into the nucleus. RNA-seq analysis of ex vivo B cells that had responded to TI-II antigen in vivo revealed a marked reduction of Myc-target gene sets in DNase1L3-deficient B cells. Expression of IRF4, a gene that Myc targets, was diminished in the ex vivo DNase1L3-deficient B cells, in which forced expression of IRF4 restored the TI-II response in vivo. These data revealed an unexpected role of DNase1L3 in a missing link between B cell receptor signaling and B cell activation in the TI-II response, giving a valuable clue to molecularly dissect this response.
The role of the microbiota in myelopoiesis during homeostasis and inflammation
Authors: Kim Yeji , Kamada Nobuhiko
Published: January 2023

Abstract The microbiota engages in the development and maintenance of the host immune system. The microbiota affects not only mucosal tissues where it localizes but also the distal organs. Myeloid cells are essential for host defense as first responders of the host immune system. Their generation, called myelopoiesis, is regulated by environmental signals, including commensal microbiota. Hematopoietic stem and progenitor cells in bone marrow can directly or indirectly sense microbiota-derived signals, thereby giving rise to myeloid cell lineages at steady-state and during inflammation. In this review, we discuss the role of commensal microorganisms in the homeostatic regulation of myelopoiesis in the bone marrow. We also outline the effects of microbial signals on myelopoiesis during inflammation and infection, with a particular focus on the development of innate immune memory. Studying the relationship between the microbiota and myelopoiesis will help us understand how the microbiota regulates immune responses at a systemic level beyond the local mucosa.
Optic tract edema in craniopharyngioma as a predictor of BRAFV600E mutation presence
Authors: Taguchi Akira , Kinoshita Yasuyuki , Kojima Masato , Amatya Vishwa J , Tominaga Atsushi , Takeshima Yukio , Arita Kazunori , Hiyama Eiso , Yamasaki Fumiyuki , Horie Nobutaka
Published: January 2023

Objective

the advent of BRAF inhibitors for preoperative treatment of craniopharyngioma has necessitated the identification of BRAFV600E status. Hence, we investigated predictors of BRAFV600E mutation in craniopharyngiomas.

Methods

this retrospective study utilized data from 30 patients who were newly diagnosed with craniopharyngioma between 2011 and 2021. Magnetic resonance imaging (MRI) and computed tomography were performed within 1 week prior to surgery. Genetic analysis for BRAF mutation was performed using the Oncomine next-generation sequencing panel or Sanger sequencing. The relationship between BRAF mutation and demographic data, endocrinological function and tumour characteristics on imaging was assessed.

Results

tumour tissue carried the BRAFV600E mutation in nine patients. There was no significant difference in age, sex, or presence of hormonal dysfunction amongst patients with and without the BRAFV600E mutation in the tumour. Most tumours with the BRAFV600E mutation were histologically categorized as papillary craniopharyngioma (P = 0.0005), and were solid (P = 0.0002) and supra-diaphragmatic (P = 0.0033) on MRI. BRAFV600E tumours were more frequently associated with optic tract edema than wild-type tumour s (55.6 vs. 0%, P = 0.0009) and all tumour s with optic tract edema carried the BRAFV600E mutation. Optic tract edema was not associated with tumour volume, cysts, or preoperative pituitary function.

Conclusions

in craniopharyngiomas, the presence of optic tract edema can predict the presence of BRAFV600E mutation with a positive predictive value of 100%. The finding should be verified in larger prospective cohorts and multivariate regression analysis.
Risk of early death in adolescents and young adults with cancer: a population-based study
Authors: Berkman Amy M , Andersen Clark R , Hildebrandt Michelle A T , Livingston J A , Green Adam L , Puthenpura Vidya , Peterson Susan K , Milam Joel , Miller Kimberly A , Freyer David R , Roth Michael E
Published: January 2023

Background

Advancements in treatment and supportive care have led to improved survival for adolescents and young adults (AYAs) with cancer; however, a subset of those diagnosed remain at risk for early death (within 2 months of diagnosis). Factors that place AYAs at increased risk of early death have not been well studied.

Methods

The Surveillance, Epidemiology, and End Results registry was used to assess risk of early death in AYAs with hematologic malignancies, central nervous system tumors, and solid tumors. Associations between age at diagnosis, sex, race, ethnicity, socioeconomic status, insurance status, rurality, and early death were assessed.

Results

A total of 268 501 AYAs diagnosed between 2000 and 2016 were included. Early death percentage was highest in patients diagnosed with hematologic malignancies (3.1%, 95% confidence interval [CI] = 2.9% to 3.2%), followed by central nervous system tumors (2.5%, 95% CI = 2.3% to 2.8%), and solid tumors (1.0%, 95% CI = 0.9% to 1.0%). Age at diagnosis, race, ethnicity, lower socioeconomic status, and insurance status were associated with increased risk of early death in each of the cancer types. For AYAs with hematologic malignancies and solid tumors, risk of early death decreased statistically significantly over time.

Conclusions

A subset of AYAs with cancer remains at risk for early death. In addition to cancer type, sociodemographic factors also affect risk of early death. A better understanding of the interplay of factors related to cancer type, treatment, and health systems that place certain AYA subsets at higher risk for early death is needed to address these disparities and improve outcomes.
Lifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis
Authors: Fu Zhuxuan , Brooks Maria Mori , Irvin Sarah , Jordan Susan , Aben Katja K H , Anton-Culver Hoda , Bandera Elisa V , Beckmann Matthias W , Berchuck Andrew , Brooks-Wilson Angela , Chang-Claude Jenny , Cook Linda S , Cramer Daniel W , Cushing-Haugen Kara L , Doherty Jennifer A , Ekici Arif B , Fasching Peter A , Fortner Renée T , Gayther Simon A , Gentry-Maharaj Aleksandra , Giles Graham G , Goode Ellen L , Goodman Marc T , Harris Holly R , Hein Alexander , Kaaks Rudolf , Kiemeney Lambertus A , Köbel Martin , Kotsopoulos Joanne , Le Nhu D , Lee Alice W , Matsuo Keitaro , McGuire Valerie , McLaughlin John R , Menon Usha , Milne Roger L , Moysich Kirsten B , Pearce Celeste Leigh , Pike Malcolm C , Qin Bo , Ramus Susan J , Riggan Marjorie J , Rothstein Joseph H , Schildkraut Joellen M , Sieh Weiva , Sutphen Rebecca , Terry Kathryn L , Thompson Pamela J , Titus Linda , van Altena Anne M , White Emily , Whittemore Alice S , Wu Anna H , Zheng Wei , Ziogas Argyrios , Taylor Sarah E , Tang Lu , Songer Thomas , Wentzensen Nicolas , Webb Penelope M ,   AOCS Group, Risch Harvey A , Modugno Francesmary
Published: January 2023

Background

The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC.

Methods

LOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26 204 control participants and 21 267 case patients from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models with expected estimates assuming 1 year of ovulation suppression has the same effect regardless of source.

Results

LOY was associated with increased EOC risk (OR per year increase = 1.014, 95% CI = 1.009 to 1.020 to OR per year increase = 1.044, 95% CI = 1.041 to 1.048). Individual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for oral contraceptive use and pregnancies were 4.45 times and 12- to 15-fold greater than expected, respectively. LOY was associated with high-grade serous, low-grade serous, endometrioid, and clear cell histotypes (ORs per year increase = 1.054, 1.040, 1.065, and 1.098, respectively) but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for high-grade serous but larger than expected for low-grade serous, endometrioid, and clear cell histotypes.

Conclusions

LOY is positively associated with nonmucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC.
A Systematic Review of Sleep Disturbances in Pediatric Inflammatory Bowel Disease
Authors: Moorman Erin L , Koskela-Staples Natalie C , Janicke David M
Published: January 2023

Objective

The current systematic review (PROSPERO ID: CRD42020220142) aims to characterize sleep health in pediatric inflammatory bowel disease (IBD) and evaluate disease-related and psychosocial prognostic factors associated with sleep disturbances in pediatric IBD.

Methods

A search of PubMed, PsycINFO, CINAHL, Web of Science, and Cochrane databases was performed. Included studies were written in English, presented original peer-reviewed research, included participants with a mean age of 8–18 years, and reported on at least one quantitative sleep outcome for children with IBD or factors impacting sleep for these children. Studies that did not report on a sleep outcome or factors influencing sleep, or only examined fatigue were excluded. Study quality was evaluated using validated quality assessment tools. The data from the included studies were extracted and synthesized across sleep health domains.

Results

Database searches yielded 122 records (total participants = 3,905). After full-text and reference/citation searches, 28 articles were included in the review. Methods used to evaluate sleep widely varied across studies and a majority of the studies were cross-sectional. Results suggest that children with IBD may not experience more frequent sleep disturbance than healthy children. Greater sleep disturbance in pediatric IBD was found to be associated with poorer psychosocial functioning and greater active disease/severe symptoms.

Conclusions

The findings from this review highlight the complex associations between sleep disturbances, inflammation, disease severity, and psychosocial functioning in children with IBD. Additional research with greater methodological rigor (e.g., use of validated sleep measures, longitudinal design, reporting of effect sizes) is warranted to further elucidate these relationships.

The current systematic review examines the existing evidence and methods of measurement of sleep disturbances in pediatric inflammatory bowel disease. We describe and evaluate factors associated with sleep disturbance in this population. The quality of evidence, strengths and weaknesses of the literature, and future directions are described.
Evolution and trends in referrals to a specialist gender identity unit in Spain over 10 years (2012-2021)
Authors: Expósito-Campos Pablo , Gómez-Balaguer Marcelino , Hurtado-Murillo Felipe , Morillas-Ariño Carlos
Published: January 2023

Background

International studies have reported an increase in referrals to gender identity units, a shift in the assigned sex ratio of adolescents, a decrease in the age at first visit, and a growing presence of individuals with nonbinary gender identities.

Aim

To investigate whether these trends are present in a Spanish sample of individuals referred to a gender identity unit over the last 10 years.

Methods

We conducted a retrospective chart review of 913 consecutive referrals to a gender identity unit between 2012 and 2021 and retrieved information regarding sex assigned at birth, age at first visit, and expressed gender identity. We stratified the patients into 5 age categories: children (<12 years), adolescents (12-17 years), young adults (18-25 years), adults (26-45 years), and older adults (>45 years). The data were analyzed via descriptive and regression analyses.

Outcomes

Outcomes included the number of annual referrals, age at first visit, assigned sex ratio, and individuals with nonbinary gender identities.

Results

The number of referrals increased 10-fold, from 18 in 2012 to 189 in 2021. The rates of increase over time were significantly more pronounced for adolescents and young adults and significantly greater for those assigned female at birth (AFAB). The age of referrals at first visit decreased, and AFAB individuals were, on average, younger than individuals assigned male at birth. The assigned sex ratio favored AFAB patients among adolescents (2.4:1) and young adults (1.75:1). Logistic regression showed that the odds of a new referral being AFAB increased by 9% per calendar year and that adolescent and young adult new referrals were significantly more likely to be AFAB. There were 21 referrals of nonbinary individuals starting in 2017, making up 6.4% of applications in 2021 and 2.9% during the last 5 years.

Clinical Implications

The evolution and trends observed in this study highlight the need for expanded resources, competent care, and careful reflection about implications for best practice.

Strengths and Limitations

This investigation involves a large sample of patients and is the first in our country to include people of all ages. However, the findings might not be generalizable to other gender identity units or the broader population of gender-diverse individuals.

Conclusion

Overall, our findings were consistent with previous international reports. We observed a marked increase in referrals, particularly among AFAB adolescents and young adults, a decreased age at first visit, and a growing presence of nonbinary individuals.
Proof theory for the logics of bringing-it-about: Ability, coalitions and means-end relationship
Authors: Dalmonte Tiziano , Grellois Charles , Olivetti Nicola
Published: January 2023

The logic of bringing-it-about (BIAT) aims to capture a notion of agency in which actions are analysed in terms of their results: ‘An agent does something’ means that the agent brings it about that something takes place. Our starting point is the basic BIAT logic as introduced by Elgesem in the ‘90s: this logic contains only a modal operator to express BIAT statements by single agents. Several extensions have been proposed by Elgesem himself and others, notably with the capability operator, coalitions of agents and means-end BIAT statements (i.e. of the form ‘the agent does B by doing A’). We first propose a variant of the neighbourhood semantics, called bi-neighbourhood semantics, for the basic BIAT logic and the mentioned extensions, in which a world is equipped by a set of pairs or neighbourhoods. Differently from the semantics defined in the literature, this reformulation is well suited for countermodel construction. We then introduce modular hypersequent calculi for all logics considered in this work. Our calculi enjoy the fundamental property of cut admissibility, from which it follows their completeness with respect to the axiomatization. Moreover, our calculi provide at the same time a decision procedure, as well as the first practical countermodel extraction procedure: from a single failed proof it is possible to build directly a finite countermodel of the formula under verification in the bi-neighbourhood semantics. By this last result, we obtain constructive proofs of the semantic completeness of the calculi and consequently of the finite model property for all logics.
Experience in Providing Ambulatory Surgery From an Expeditionary Fast Transport Mobile and Rapidly Deployable Expeditionary Medical Unit During Continuing Promise 2018
Authors: Garry Conor B , Middlebrooks Reginald , Moore John D , Souza Jason M , Sayles Timothy E , Ricca Robert L
Published: January 2023

Introduction

This article describes the surgical component of the Continuing Promise 2018 (CP-18) medical training and military cooperation mission. We report on the surgical experience and lessons learned from performing peacetime ambulatory surgeries in a tent-based facility constructed on partner nation territory.

Methods

This CP mission was unique in utilizing a land-based expeditionary surgical facility. Institutional Review Board approval was obtained to collect prospective deidentified patient data and aggregate information on all surgical cases performed. Specific aims of this study included describing surgical patient characteristics and evaluating conservatively selected cases performed in this environment. Body mass index (BMI) was used as a crude screening tool for perioperative risk to assist patient selection. Our secondary aim was to report lessons learned from preparation, logistics, and host nation exchanges. The team coordinated medical credentialing and documentation of all medical supplies with each host nation. Advance teams collaborated with local physicians in country to arrange training exchanges and identify surgical candidates.

Results

The mission was conducted from February to April 2018. Only two of five planned partner nation visits were completed. The surgical facility supported 78 procedures over 14 surgical days, averaging over six cases performed per core surgical day. Patients were predominantly female, with a mean age of 25.4 and a mean BMI of 31.1. The average surgical time was 37.5 minutes, the average anesthesia time was 70 minutes, and the average recovery time was 47.6 minutes. No significant complications or adverse events were noted.

Conclusions

CP-18 was the first CP mission to perform elective ambulatory surgery on foreign soil using a tent-based facility in a noncombat, nondisaster environment instead of a hospital or amphibious ship. This mission demonstrated that such a facility may be employed to safely perform low-risk ambulatory surgeries on carefully selected patients. The Expeditionary Medical Unit, coupled with the fast transport vessel enabled rapid expeditionary surgical facility setup with significant military and disaster relief applications. Expansion of surgical indications should be performed carefully and deliberately to avoid complications and damage to international relationships.
Residuals of an equilibrium model for the galaxy reveal a state of disequilibrium in the Solar Neighbourhood
Authors: Li Haochuan , Widrow Lawrence M
Published: January 2023

We simultaneously model the gravitational potential and phase space distribution function (DF) of giant stars near the Sun using the Gaia DR2 radial velocity catalogue. We assume that the Galaxy is in equilibrium and is symmetric about both the spin axis of the disc and the Galactic mid-plane. The potential is taken as a sum of terms that nominally represent contributions from the gas and stellar discs, the bulge, and the dark matter halo. Our model for the DF comprises two components to account for a mix of thin and thick disc stars. Each component is described by an analytic function of the energy, the spin angular momentum, and the vertical energy, in accord with Jeans theorem. We present model predictions for the radial and vertical forces within $\sim 2\, {\rm kpc}$ of the Sun, highlighting the rotation curve, the asymmetric drift curve, and the vertical force profile. We then show residuals for star counts in the R–z and z–vz planes as well as maps of the mean radial and azimuthal velocities in the z–vz plane. Using our model for the potential, we map the star count residuals in action-frequency-angle coordinates. The Gaia phase spiral, velocity arches, bending waves, and some of the known moving groups appear as well-defined features in these maps.
A theoretical study of propynal under interstellar conditions and beyond, covering low-frequency infrared spectra, spectroscopic constants, and hot bands
Authors: Tschöpe Martin , Rauhut Guntram
Published: January 2023

From an astrochemical point of view, propynal is a complex organic molecule. Moreover, it is a potential candidate for the formation of prebiotic propanal and propenal. Therefore, this molecule is of particular interest for astrochemical investigations. As it has been detected in the interstellar medium, it is of high relevance in this field of research. Although experimental data are available for the vibrational fundamental bands and rotational constants, experimental data for vibrational overtones and combination bands are scarce and fairly old. Additionally, high-level ab initio calculations are also not reported. In this work, we provide accurate quantum chemical calculations as well as a detailed analysis of vibrational and rovibrational properties for this molecule. The low-frequency spectrum up to $350\, \,\,\text{cm}^{-1}$ has been studied for temperatures between 10 and $300\, \text{K}$. For the same temperature range, partition functions are provided. Furthermore, the impact of hot bands up to room temperature has been investigated. A comparison of our results with experimental data is provided for the rotational constants, geometrical parameters, and a rovibrational spectrum. The underlying potential energy surface within these calculations is based on explicitly correlated coupled-cluster theory and includes up to four-mode coupling terms within an n-mode expansion. The vibrational and rovibrational calculations rely on vibrational and rovibrational configuration interaction theories, respectively.
The nucleosome unwrapping free energy landscape defines distinct regions of transcription factor accessibility and kinetics
Authors: Donovan Benjamin T , Luo Yi , Meng Zhiyuan , Poirier Michael G
Published: January 2023

Transcription factors (TF) require access to target sites within nucleosomes to initiate transcription. The target site position within the nucleosome significantly influences TF occupancy, but how is not quantitatively understood. Using ensemble and single-molecule fluorescence measurements, we investigated the targeting and occupancy of the transcription factor, Gal4, at different positions within the nucleosome. We observe a dramatic decrease in TF occupancy to sites extending past 30 base pairs (bp) into the nucleosome which cannot be explained by changes in the TF dissociation rate or binding site orientation. Instead, the nucleosome unwrapping free energy landscape is the primary determinant of Gal4 occupancy by reducing the Gal4 binding rate. The unwrapping free energy landscape defines two distinct regions of accessibility and kinetics with a boundary at 30 bp into the nucleosome where the inner region is over 100-fold less accessible. The Gal4 binding rate in the inner region no longer depends on its concentration because it is limited by the nucleosome unwrapping rate, while the frequency of nucleosome rewrapping decreases because Gal4 exchanges multiple times before the nucleosome rewraps. Our findings highlight the importance of the nucleosome unwrapping free energy landscape on TF occupancy and dynamics that ultimately influences transcription initiation.
Upstream of N-Ras C-terminal cold shock domains mediate poly(A) specificity in a novel RNA recognition mode and bind poly(A) binding protein
Authors: Hollmann Nele Merret , Jagtap Pravin Kumar Ankush , Linse Johanna-Barbara , Ullmann Philip , Payr Marco , Murciano Brice , Simon Bernd , Hub Jochen S , Hennig Janosch
Published: January 2023

RNA binding proteins (RBPs) often engage multiple RNA binding domains (RBDs) to increase target specificity and affinity. However, the complexity of target recognition of multiple RBDs remains largely unexplored. Here we use Upstream of N-Ras (Unr), a multidomain RBP, to demonstrate how multiple RBDs orchestrate target specificity. A crystal structure of the three C-terminal RNA binding cold-shock domains (CSD) of Unr bound to a poly(A) sequence exemplifies how recognition goes beyond the classical ππ-stacking in CSDs. Further structural studies reveal several interaction surfaces between the N-terminal and C-terminal part of Unr with the poly(A)-binding protein (pAbp). All interactions are validated by mutational analyses and the high-resolution structures presented here will guide further studies to understand how both proteins act together in cellular processes.
Cancer-associated SMARCAL1 loss-of-function mutations promote alternative lengthening of telomeres and tumorigenesis in telomerase-negative glioblastoma cells
Authors: Liu Heng , Xu Cheng , Diplas Bill H , Brown Alexandrea , Strickland Laura M , Yao Haipei , Ling Jinjie , McLendon Roger E , Keir Stephen T , Ashley David M , He Yiping , Waitkus Matthew S
Published: January 2023

Background

Telomere maintenance mechanisms are required to enable the replicative immortality of malignant cells. While most cancers activate the enzyme telomerase, a subset of cancers uses telomerase-independent mechanisms termed alternative lengthening of telomeres (ALT). ALT occurs via homology-directed-repair mechanisms and is frequently associated with ATRX mutations. We previously showed that a subset of adult glioblastoma (GBM) patients with ATRX-expressing ALT-positive tumors harbored loss-of-function mutations in the SMARCAL1 gene, which encodes an annealing helicase involved in replication fork remodeling and the resolution of replication stress. However, the causative relationship between SMARCAL1 deficiency, tumorigenesis, and de novo telomere synthesis is not understood.

Methods

We used a patient-derived ALT-positive GBM cell line with native SMARCAL1 deficiency to investigate the role of SMARCAL1 in ALT-mediated de novo telomere synthesis, replication stress, and gliomagenesis in vivo.

Results

Inducible rescue of SMARCAL1 expression suppresses ALT indicators and inhibits de novo telomere synthesis in GBM and osteosarcoma cells, suggesting that SMARCAL1 deficiency plays a functional role in ALT induction in cancers that natively lack SMARCAL1 function. SMARCAL1-deficient ALT-positive cells can be serially propagated in vivo in the absence of detectable telomerase activity, demonstrating that the SMARCAL1-deficient ALT phenotype maintains telomeres in a manner that promotes tumorigenesis.

Conclusions

SMARCAL1 deficiency is permissive to ALT and promotes gliomagenesis. Inducible rescue of SMARCAL1 in ALT-positive cell lines permits the dynamic modulation of ALT activity, which will be valuable for future studies aimed at understanding the mechanisms of ALT and identifying novel anticancer therapeutics that target the ALT phenotype.
Alternative 3′-untranslated regions regulate high-salt tolerance ofSpartina alterniflora
Authors: Wang Taotao , Ye Wenbin , Zhang Jiaxiang , Li Han , Zeng Weike , Zhu Sheng , Ji Guoli , Wu Xiaohui , Ma Liuyin
Published: January 2023

High-salt stress continues to challenge the growth and survival of many plants. Alternative polyadenylation (APA) produces mRNAs with different 3′-untranslated regions (3′ UTRs) to regulate gene expression at the post-transcriptional level. However, the roles of alternative 3′ UTRs in response to salt stress remain elusive. Here, we report the function of alternative 3′ UTRs in response to high-salt stress in S. alterniflora (Spartina alterniflora), a monocotyledonous halophyte tolerant of high-salt environments. We found that high-salt stress induced global APA dynamics, and ∼42% of APA genes responded to salt stress. High-salt stress led to 3′ UTR lengthening of 207 transcripts through increasing the usage of distal poly(A) sites. Transcripts with alternative 3′ UTRs were mainly enriched in salt stress-related ion transporters. Alternative 3′ UTRs of HIGH-AFFINITY K+ TRANSPORTER 1 (SaHKT1) increased RNA stability and protein synthesis in vivo. Regulatory AU-rich elements were identified in alternative 3′ UTRs, boosting the protein level of SaHKT1. RNAi-knock-down experiments revealed that the biogenesis of 3′ UTR lengthening in SaHKT1 was controlled by the poly(A) factor CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR 30 (SaCPSF30). Over-expression of SaHKT1 with an alternative 3′ UTR in rice (Oryza sativa) protoplasts increased mRNA accumulation of salt-tolerance genes in an AU-rich element-dependent manner. These results suggest that mRNA 3′ UTR lengthening is a potential mechanism in response to high-salt stress. These results also reveal complex regulatory roles of alternative 3′ UTRs coupling APA and regulatory elements at the post-transcriptional level in plants.
Explaining the physics of transfer learning in data-driven turbulence modeling
Authors: Subel Adam , Guan Yifei , Chattopadhyay Ashesh , Hassanzadeh Pedram
Published: January 2023

Transfer learning (TL), which enables neural networks (NNs) to generalize out-of-distribution via targeted re-training, is becoming a powerful tool in scientific machine learning (ML) applications such as weather/climate prediction and turbulence modeling. Effective TL requires knowing (1) how to re-train NNs? and (2) what physics are learned during TL? Here, we present novel analyses and a framework addressing (1)–(2) for a broad range of multi-scale, nonlinear, dynamical systems. Our approach combines spectral (e.g. Fourier) analyses of such systems with spectral analyses of convolutional NNs, revealing physical connections between the systems and what the NN learns (a combination of low-, high-, band-pass filters and Gabor filters). Integrating these analyses, we introduce a general framework that identifies the best re-training procedure for a given problem based on physics and NN theory. As test case, we explain the physics of TL in subgrid-scale modeling of several setups of 2D turbulence. Furthermore, these analyses show that in these cases, the shallowest convolution layers are the best to re-train, which is consistent with our physics-guided framework but is against the common wisdom guiding TL in the ML literature. Our work provides a new avenue for optimal and explainable TL, and a step toward fully explainable NNs, for wide-ranging applications in science and engineering, such as climate change modeling.
Is There Investment Value in the Soft-Dollar Arrangement? Evidence from Mutual Funds
Authors: Gokkaya Sinan , Liu Xi , Pool Veronika Krepely , Xie Fei , Zhang Jinfan
Published: January 2023

Combining novel data on analyst employment history and mutual fund commission payments, we show that client funds generate higher returns on stocks for which they have access to research by industry expert analysts. The outperformance is greater when funds are more important clients and cannot be attributed to tipping. Client funds place modestly higher weights on stocks covered by industry expert analysts and allocate more commissions to brokers providing such coverage. For identification, we exploit exogenous analyst coverage disruptions. Our findings contribute to the debate on whether mutual funds obtain any investment value from access to analysts through the soft-dollar arrangement.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Detection of a rare variant inPSTPIP1through three generations in a family with an initial diagnosis of FMF/MKD-overlapping phenotype
Authors: Özkılınç Önen Merve , Onat Umut İ , Uğurlu Serdal , Timuçin Ahmet C , Öz Arslan Devrim , Everest Elif , Özdoğan Huri , Tahir Turanlı Eda
Published: January 2023

Objective

The presence of FMF cases without MEFV (MEFV innate immunity regulator, pyrin) pathogenic variants led us to search for other genes’ involvement in the disease development. Here, we describe the presence of genetic heterogeneity in a three-generation family with an FMF/mevalonate kinase deficiency (MKD)-overlapping phenotype without MEFV/MVK (mevalonate kinase) pathogenic variants.

Method

Targeted sequencing revealed a rare, fully penetrant variant in PSTPIP1 (p.Arg228Cys, rs781341816). Computational stability analyses of PSTPIP1 protein were performed. PSTPIP1-pyrin protein interaction was examined by immunoprecipitation and immunoblotting in peripheral blood mononuclear cells (PBMCs) of patients and healthy controls. PBMCs were cultured, and inflammation was induced by LPS+ATP treatment, followed by protein level measurements of caspase-1, IL1ß, pyrin and PSTPIP1 in cell lysates and mature caspase-1 and mature IL1ß in supernatants.

Results

The conserved, rare (GnomAD, 0.000028) PSTPIP1 p.Arg228Cys variant, previously reported in ClinVar as a variant with uncertain significance, showed complete penetrance in the family presenting an autosomal dominant pattern. Computational analyses showed a potentially destabilizing effect of the variant on PSTPIP1 protein. Accordingly, PSTPIP1-pyrin interaction was increased in patients harboring the variant, which resulted in elevated levels of mature caspase-1 and IL1ß in the inflammation-induced patient samples.

Conclusions

Unlike previously described cases with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA)-associated PSTPIP1 variants, our patients with the p.Arg228Cys variant presented with an FMF/MKD-overlapping phenotype. As additional data on the genetic heterogeneity in the variable clinical spectrum of autoinflammatory syndromes, we suggest that the p.Arg228Cys variant in PSTPIP1 is related to inflammation responses through strong PSTPIP1-pyrin interaction and pyrin inflammasome activation.
Destroying Democracy for the People: The Economic, Social, and Political Consequences of Populist Rule, 1990 to 2017
Authors: Cole Wade M , Schofer Evan
Published: January 2023

The recent populist wave has raised questions about the implications of populism for democracy. Some scholars express optimism that populism may be a source of democratic revitalization, bringing about sweeping changes in accordance with the majority will. More often, populism is viewed as a threat to liberal democracy, combining calls for radical change with disdain for core democratic institutions and norms. We consider the possibility that these outcomes may not be mutually exclusive and develop a conceptual typology for understanding the consequences of populist rule. We then use cross-national panel fixed-effects models to analyze the effects of populist leadership between 1990 and 2017. We first examine whether populists have economic and social effects in line with their core aspirations. Left-wing populists are quite effective at implementing their agenda: they reduce income inequality, regulate markets, and incorporate marginalized groups. Right-wing populists are also fairly impactful: for instance, they raise tariffs, cut taxes, and restrict the rights of women and gay people. However, populists of all stripes are associated with the rapid and severe erosion of liberal democratic institutions. Populists, we conclude, often destroy democracy in the name of the people.
A process for converting an in-person training to increase church capacity to implement physical activity and healthy eating practices and policies to an online format
Authors: Wilcox Sara , Saunders Ruth P , Stucker Jessica , Kaczynski Andrew T , Day Kelsey R , Kinnard Deborah , Decker Lindsay , Bernhart John A
Published: January 2023

The implementation of evidence-based public health programs into practice is critical for improving health, but trainings for organizational change agents are often not scalable.

To describe the process of converting a training that targets faith-based organizational capacity development from an in-person to an online format.

We engaged in an iterative process to convert the training delivery mode from in-person to online that included assessing stakeholder support, consulting the literature on best practices, seeking a design team, consolidating content, designing engaging lessons, and building an online site. Feedback from end-users and other audiences was incorporated throughout. Pilot participants with characteristics like intended training users were then recruited via community and faith-based partner networks. They rated their agreement with statements about the effectiveness as well as design and functionality of each lesson and the overall training (1 = strongly disagree, 5 = strongly agree) and participated in a structured follow-up interview.

Nine pilot participants (representing 9 churches in 7 states; 6 African American, 5 with health ministries) rated the online lessons favorably (all ratings ≥ 4.5). Most (90.4%) perceived the lesson duration to be “just right” and spent 52.5 ± 9.9 minutes/lesson. Participants evaluated the overall training positively (all ratings ≥ 4.7). Lesson content, resources, multimedia, and program ideas were most-liked aspects of lessons, while content, staff responsiveness, discussion board, and pace were most-liked aspects of the overall training in open-ended and interview responses.

This paper shares a replicable process for converting training modalities from in-person to online with the goal of increased scalability.