bluuebunny/crossref_metadata_2025 huggingface dataset:
Right ventricular to pulmonary arterial coupling as a predictor of survival in patients undergoing mitral valve surgery for mitral regurgitation
Authors: Chehab Omar , Long Edouard , Androshchuk Vitaly , Gill Harminder , Avlonitis Vassilios , Bosco Paolo , Lucchese Gianluca , Patterson Tiffany , Redwood Simon , Rajani Ronak
Published: November 2024

OBJECTIVES

Right ventricular-to-pulmonary artery coupling has been associated with outcomes in mitral regurgitation treated by transcatheter approaches. We evaluated right ventricular-to-pulmonary artery coupling as a predictor of survival and postoperative length of hospital stay (LOS) in patients with mitral regurgitation undergoing mitral valve surgery.

METHODS

In this retrospective analysis (median follow-up: 5.8 years), right ventricular-to-pulmonary artery coupling was quantified as the ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) using transthoracic echocardiography. Receiver operating characteristic curve analysis was used to determine the optimum cut-point of TAPSE/PASP to predict all-cause mortality, and the study population was dichotomized according to this value. The primary end point was all-cause mortality. A secondary end point of LOS was also assessed.

RESULTS

Out of 142 patients (median age: 67, female: 49%), 35 showed impaired coupling at baseline (TAPSE/PASP ≤0.35). Patients with TAPSE/PASP ≤0.35 had higher absolute mortality (37% vs 8%, P < 0.001) and longer LOS (7 days vs 9 days, P = 0.04). Kaplan–Meier analysis revealed lower survival in patients with TAPSE/PASP ≤0.35 (log-rank: P < 0.0001). In multivariable Cox regression, TAPSE/PASP ≤0.35 was the most significant predictor of all-cause mortality (hazard ratio: 3.69, 95% confidence interval 1.31–10.1, P = 0.011), alongside chronic obstructive pulmonary disease and estimated glomerular filtration rate. TAPSE/PASP ≤0.35 was associated with significantly increased LOS (β: 4.6, 95% confidence interval 0.66–8.5, P = 0.022) alongside left ventricular ejection fraction, mitral valve replacement and urgent operation.

CONCLUSIONS

In mitral regurgitation patients undergoing mitral valve surgery, TAPSE/PASP ≤0.35 is associated with increased mortality and LOS. Further validation is indicated in larger, prospective cohorts.
Reverse-engineering the Venus figurines: An eco-life-course hypothesis for the aetiology of obesity in the Palaeolithic
Authors: Wells Jonathan C K , Williams Frank L’Engle , Desoye Gernot
Published: November 2024

Evolutionary perspectives on obesity have been dominated by genetic frameworks, but plastic responses are also central to its aetiology. While often considered a relatively modern phenomenon, obesity was recorded during the Palaeolithic through small statuettes of the female form (Venus figurines). Even if the phenotype was rare, these statuettes indicate that some women achieved large body sizes during the last glacial maximum, a period of nutritional stress. To explore this paradox, we develop an eco-life-course conceptual framework that integrates the effects of dietary transitions with intergenerational biological mechanisms. We assume that Palaeolithic populations exposed to glaciations had high lean mass and high dietary protein requirements. We draw on the protein leverage hypothesis, which posits that low-protein diets drive overconsumption of energy to satisfy protein needs. We review evidence for an increasing contribution of plant foods to diets as the last glacial maximum occurred, assumed to reduce dietary protein content. We consider physiological mechanisms through which maternal overweight impacts the obesity susceptibility of the offspring during pregnancy. Integrating this evidence, we suggest that the last glacial maximum decreased dietary protein content and drove protein leverage, increasing body weight in a process that amplified across generations. Through the interaction of these mechanisms with environmental change, obesity could have developed among women with susceptible genotypes, reflecting broader trade-offs between linear growth and adiposity and shifts in the population distribution of weight. Our approach may stimulate bioarchaeologists and paleoanthropologists to examine paleo-obesity in greater detail and to draw upon the tenets of human biology to interpret evidence.
Hiding in plain sight: the Y chromosome and its reinvigorated role in evolutionary processes
Authors: van der Bijl Wouter , Mank Judith E
Published: November 2024

Recent methodological approaches have expanded our understanding of Y chromosome sequence, revealed unexpected Y diversity, and sparked a growing realization of its importance in evolutionary processes. To fully understand the diversity and importance of the Y chromosome, we suggest the need to move from a holotype Y chromosome sequence, based on a single individual and meant to represent the species, to a thorough understanding of Y chromosome haplotype diversity, its phenotypic implications, and its phylogeographic distribution. Additionally, the Y chromosome may play an important role in two key rules of speciation that have otherwise been attributed to the X, namely Haldane’s Rule and the Large-X Effect. Emerging genomic tools and analytical approaches are just now giving us the means to ask how important this small, often forgotten region of the genome is in evolutionary processes.
Masu salmon species complex relationships and sex chromosomes revealed from analyses of the masu salmon (Oncorhynchus masou masou) genome assembly
Authors: Christensen Kris A , Flores Anne-Marie , Joshi Jay , Shibata Kiko , Fujimoto Takafumi , Koop Ben F , Devlin Robert H
Published: November 2024

Masu salmon (Oncorhynchus masou) are the only Pacific salmon endemic to Asia. Some researchers prefer to categorize these salmon into 4 subspecies (masu—Oncorhynchus masou masou, amago—Oncorhynchus masou ishikawae, Biwa—Oncorhynchus masou subsp., and Formosan—Oncorhynchus masou formosanus), while others prefer individual species designations. Even though the masu salmon fishery is thousands of years old, classification of the diversity within the masu salmon species complex remains elusive. In this study, a genetic map and reference genome assembly were generated for 1 species/subspecies (masu) to provide resources for understanding the species complex. In O. m. masou, the sex chromosome was determined to be chromosome 7. Resequenced genomes from 2 other putative subspecies (amago and Biwa) provided evidence that they do not share the same sex chromosome. Principal component and admixture analyses clustered the amago and Biwa salmon close together. This supported previous findings of a close relationship between amago and Biwa salmon and a more distant relationship to masu salmon for both. Additional analyses of the masu salmon species complex will benefit from using the new reference genome assembly.
Advanced glycation end-products and metabolomics are independently associated with frailty: the longitudinal Doetinchem Cohort Study
Authors: Kuiper Lieke M , Picavet H Susan J , Rietman M Liset , Dollé Martijn E T , Verschuren W M Monique
Published: November 2024

Skin autofluorescence (SAF), reflecting advanced glycation end-products’ accumulation in tissue, has been proposed as a non-invasive aging biomarker. Yet, SAF has not been compared to well-established blood-based aging biomarkers such as MetaboHealth in association with frailty. Furthermore, no previous study determined the longitudinal association of SAF with frailty.

We used 2382 Doetinchem Cohort Study participants’ (aged 46.0 to 85.4) cross-sectional data, of whom 1654 had longitudinal SAF measurements. SAF was measured using the AGE reader™. MetaboHealth was calculated on 1H-NMR-metabolomics. Linear regressions were used for the associations of SAF and MetaboHealth on the 36-deficit frailty index and logistic regressions for being pre-frail or frail as determined by the frailty phenotype. Longitudinal associations were determined by an interaction term between age and SAF in a linear mixed model.

SAF and MetaboHealth were associated with higher odds of pre-frailty (odd ratios per standard deviation SAF: 1.21(1.10;1.32), MetaboHealth: 1.35(1.24;1.49)) and frailty (SAF: 1.70(1.41;2.06), MetaboHealth: 1.90(1.57;2.32)). When mutually adjusted, both aging biomarkers remained associated with pre-frailty (SAF: 1.16(1.05;1.27), MetaboHealth 1.33(1.21;1.46)) and frailty (SAF: 1.52(1.25;1.85), MetaboHealth: 1.75(1.43;2.14)). Additionally, SAF and MetaboHealth were associated with higher frailty index scores (percentage increase per standard deviation SAF:1.35(1.00;1.70), MetaboHealth: 1.87(1.54;2.20)), also after mutual adjustment (SAF: 1.02(0.68;1.37), MetaboHealth: 1.69(1.35;2.02)). SAF was also longitudinally associated with the frailty index (percentage per unit/year increase 0.12(0.07;0.16)).

The mutual independence of SAF and MetaboHealth implies they capture distinct aspects of the aging process. Altogether, these findings emphasize SAF’s clinical potential as an age-related decline biomarker, which could be further enhanced when combined with MetaboHealth.
Ground motion characteristics of subshear and supershear ruptures in the presence of sediment layers
Authors: Abdelmeguid Mohamed , Elbanna Ahmed , Rosakis Ares
Published: November 2024

We investigate the impact of sediment layers on ground motion characteristics during subshear and supershear rupture growth. Our findings suggest that sediment layers may lead to local supershear propagation, affecting ground motion, especially in the fault parallel (FP) direction. In contrast to homogeneous material models, we find that in the presence of sediment layers, a larger fault normal (FN) compared to FP particle velocity jump, reflects shear propagation at depth but does not rule out shallow supershear propagation. Conversely, a large FP compared to FN particle velocity jump indicates supershear propagation at depth. In the presence of a shallow layer, we also uncover a non-monotonic behaviour in the sediment’s influence on supershear transition and ground motion characteristics. During supershear propagation at depth we observe that sediment layers contribute to enhancing FP velocity pulses while minimally affecting the FN component. Furthermore, in the limit of global supershear propagation we identify local supersonic propagation within the sediment layers that significantly alters the velocity field around the rupture tip as observed on the free surface, creating both dilatational and shear Mach cones. In all our models with sediments we also find a significant enhancement in the fault vertical component of ground velocity. This could have particular implications for hazard assessments, such as in applications related to linear infrastructure, or a higher propensity to tsunami wave generation. Our research unravels the importance of considering heterogeneous subsurface material distribution in our physical models as they can have drastic implications on earthquake source physics.
Market segmentation by profit status: evidence from hospice
Authors: Rosenkranz David A , White Lindsay , Sun Chuxuan , Miller Katherine E M , Coe Norma B
Published: November 2024

How do referral networks and medical conditions determine where patients get care? We study this question in the US Hospice Industry, where for-profit hospice programs enroll more long-term care patients and more patients with Alzheimer’s disease and related dementia. We find that for-profit hospice enrollees have 23% longer lifetime lengths-of-stay in hospice care than not for-profit hospice enrollees with the same medical conditions, institutional referral source, county of residence, and enrollment year. This and other differences in their end-of-life health care utilization suggest that hospice market segmentation is the result of a patient-specific selection mechanism that is partially independent of institutional barriers to hospice care.
Immune system regulation of physiological and pathological aspects of the ovarian follicle pool throughout the female reproductive lifespan
Authors: Cacciottola L , Camboni A , Dolmans M M
Published: November 2024

The immune system plays a major role in ovarian physiology by regulating the ovarian follicle pool through complex signaling of different growth factors, cytokines, and chemokines. These may promote follicle activation and further growth but could also trigger follicle atresia and clearance of aging or damaged cells within the ovarian cortex. Moreover, extraglandular steroidogenesis potentially occurring in different immune cells like macrophages and natural killer cells might be another way of modulating follicle growth. Ovarian macrophages have recently been found to contain two different populations, namely resident macrophages and monocyte-derived cells, with potentially different roles. The immune system also plays a role in the development of pathological conditions, including premature ovarian insufficiency (POI). Indeed, autoimmune activation against various ovarian antigen targets results in lymphocytic oophoritis mainly targeting early growing follicles, but later leading to complete follicle pool depletion. Immune-mediated ovarian damage may also be caused by viral infection or be the consequence of iatrogenic damage. Certain novel cancer immunotherapies like checkpoint inhibitors have recently been shown to induce ovarian reserve damage in a murine model. Studies are needed to corroborate these findings and further investigate the potential of newly developed immunotherapies to treat POI. Technological advances such as single-cell analyses of less represented cell populations like immune cells inside the ovary are now contributing to valuable new information, which will hopefully lead to the development of new therapeutic strategies for women with fertility issues.
Deep learning-based classifier for carcinoma of unknown primary using methylation quantitative trait loci
Authors: Walker Adam , Fang Camila S , Schroff Chanel , Serrano Jonathan , Vasudevaraja Varshini , Yang Yiying , Belakhoua Sarra , Faustin Arline , William Christopher M , Zagzag David , Chiang Sarah , Acosta Andres Martin , Movahed-Ezazi Misha , Park Kyung , Moreira Andre L , Darvishian Farbod , Galbraith Kristyn , Snuderl Matija
Published: November 2024

Cancer of unknown primary (CUP) constitutes between 2% and 5% of human malignancies and is among the most common causes of cancer death in the United States. Brain metastases are often the first clinical presentation of CUP; despite extensive pathological and imaging studies, 20%-45% of CUP are never assigned a primary site. DNA methylation array profiling is a reliable method for tumor classification but tumor-type-specific classifier development requires many reference samples. This is difficult to accomplish for CUP as many cases are never assigned a specific diagnosis. Recent studies identified subsets of methylation quantitative trait loci (mQTLs) unique to specific organs, which could help increase classifier accuracy while requiring fewer samples. We performed a retrospective genome-wide methylation analysis of 759 carcinoma samples from formalin-fixed paraffin-embedded tissue samples using Illumina EPIC array. Utilizing mQTL specific for breast, lung, ovarian/gynecologic, colon, kidney, or testis (BLOCKT) (185k total probes), we developed a deep learning-based methylation classifier that achieved 93.12% average accuracy and 93.04% average F1-score across a 10-fold validation for BLOCKT organs. Our findings indicate that our organ-based DNA methylation classifier can assist pathologists in identifying the site of origin, providing oncologists insight on a diagnosis to administer appropriate therapy, improving patient outcomes.
Causal mediation analysis: selection with asymptotically valid inference
Authors: Jones Jeremiah , Ertefaie Ashkan , Strawderman Robert L
Published: November 2024

Researchers are often interested in learning not only the effect of treatments on outcomes, but also the mechanisms that transmit these effects. A mediator is a variable that is affected by treatment and subsequently affects outcome. Existing methods for penalized mediation analyses may lead to ignoring important mediators and either assume that finite-dimensional linear models are sufficient to remove confounding bias, or perform no confounding control at all. In practice, these assumptions may not hold. We propose a method that considers the confounding functions as nuisance parameters to be estimated using data-adaptive methods. We then use a novel regularization method applied to this objective function to identify a set of important mediators. We consider natural direct and indirect effects as our target parameters. We then proceed to derive the asymptotic properties of our estimators and establish the oracle property under specific assumptions. Asymptotic results are also presented in a local setting, which contrast the proposal with the standard adaptive lasso. We also propose a perturbation bootstrap technique to provide asymptotically valid postselection inference for the mediated effects of interest. The performance of these methods will be discussed and demonstrated through simulation studies.
Mixed functional tumor of the left adrenal as a cause of palpitations, surgical management. Case report
Authors: Muñoz-Palomeque Santiago , Aguayo-Vistin William , Molina Gabriel A , Bastidas-Arévalo Zanny , Herrera Gonzalez Jaime Paul , Gordon Christian I
Published: November 2024

Compound pheochromocytoma refers to a rare adrenal tumor that includes neuroblastic components and is a rare catecholamine-producing tumor from chromaffin cells, typically found in the adrenal medulla. It usually presents with symptoms like tachycardia, headache, and intermittent diaphoresis, although its clinical manifestations can vary. Diagnosis involves biochemical studies and imaging such as catecholamines, metanephrines, CT scans, and positron emission tomography (PET). The surgical management is the definitive, being the laparoscopic approach of choice in most cases. This case report discusses a 45-year-old male who presented with tachycardia and palpitations, diagnosed with left pheochromocytoma exhibiting neuroblastoma differentiation, surgically treated through anterior laparoscopy without any trans-surgical complications and with low bleeding. Postoperative recovery was uneventful, and pathology confirmed the diagnosis. Timely diagnosis and surgical removal are crucial, with laparoscopy being the preferred approach for tumor resection.
A complication of recurrent artery of Heubner infarction after resection of a giant thrombotic aneurysm in the anterior cerebral artery A2 segment: case report
Authors: Fu Kuan-Hao , Chen Pin-Yuan , Yan Jiun-Lin
Published: November 2024

Giant thrombotic aneurysms of the anterior cerebral artery (ACA) are rare and pose significant challenges due to their variable clinical presentations. While complications following surgical interventions for these aneurysms are known, they have not been fully characterized. We present a novel case of postoperative infarction in the recurrent artery of Heubner (RAH) following resection of a thrombotic giant aneurysm in the ACA. A 53-year-old man with no prior systemic illnesses presented with progressive weakness in his left hand and foot, along with slurred speech. Imaging studies revealed a giant thrombotic aneurysm in the proximal A2 segment of the right ACA, which was completely occluded. Additionally, a chronic infarction was identified in the territory of the right ACA. The patient underwent successful surgical resection of the aneurysm. However, he subsequently developed an infarction in the RAH territory, a complication rarely reported in the literature. This case highlights the importance of comprehensive preoperative evaluation and underscores the need to anticipate and manage potential complications following surgery.
Treatment of multiple vulvar angiokeratomas using long-pulsed 1064-nm Nd:Yag laser: a case report
Authors: Mancuso Fabrizio Rocco , Cipollini Emanuele Maria , Zingoni Tiziano , Fusco Irene , Sannino Mario , Cannarozzo Giovanni
Published: November 2024

The purpose of this clinical case was to test the efficacy and safety of the long-pulsed 1064-nm neodymium-YAG laser in the treatment of multiple angiokeratomas on the labia majora of the vulva. Benign vascular neoplasms known as angiokeratomas are characterized by well-defined, hyperkeratotic, reddish-black papules, or plaques. The patient underwent one treatment session with a long-pulsed 1064-nm neodymium-YAG laser. A clinical photographic assessment was performed immediately after the laser session and at 14 days follow-up. At the follow-up appointment, the patient reported no significant discomfort and physical examination revealed complete resolution of all angiokeratomas. The skin of the labia majora appeared healthy, with no visible scarring or pigmentation changes. The patient expressed high satisfaction with the cosmetic outcome. This case supports the use of laser systems for managing angiokeratomas in delicate areas like the genital region, providing significant aesthetic improvement and patient satisfaction.
Mechanical jejunal obstruction caused by a migrated intragastric balloon: a case report
Authors: Ghali Mohamed S , Elhassan Osman O , Al-Zoubi Raed M
Published: November 2024

An intragastric balloon is often used as a temporary solution for weight loss. It is endoscopically placed into the stomach and filled with air or saline to encourage fullness and reduce meal intake. A 23-year-old female with a history of a gastric balloon procedure presented to the emergency department with generalized abdominal pain and recurrent vomiting. Initial imaging with ultrasound and computed tomography scans revealed a collapsed migrated gastric balloon causing a small bowel obstruction. Despite initial conservative management, the patient required surgical intervention, which involved laparoscopic exploration, mini laparotomy, and enterotomy to extract the migrated balloon. Postoperatively, the patient had an uneventful recovery and was discharged with a stable condition. This case underscores the importance of considering device-related complications in patients with gastric balloons presenting with gastrointestinal symptoms and highlights the need for prompt imaging and appropriate surgical management.

Intragastric balloon migration leading to small bowel obstruction is a rare but serious complication that should be considered in patients presenting with abdominal pain and vomiting following a gastric balloon procedure. Prompt imaging and surgical intervention are crucial for effective management and favorable outcomes.
“I Fell Off a Ladder, and My Back Really Hurts.”: Acute Trauma in a 38-Year-Old Male
Authors: Oyekan Anthony A. , Ridolfi Dominic , Gibbs Christopher , Shaw Jeremy D.
Published: November 2024

Vertebral burst fractures are common in high-energy trauma. Presenting symptoms include severe back pain, leg symptoms, and neurological deficits. It is a severe injury caused by pure axial compression that may require acute operative intervention. When conceptualizing the spine in 3 columns, burst fractures involve the anterior and middle columns and can result in retropulsion of bone, which can cause spinal stenosis and associated neurological deficits. Initial imaging with plain radiographs of the lumbar spine should be done, along with radiographs of the cervical and thoracic spine as 10% of such patients have multiple burst fractures. Magnetic resonance imaging (MRI) or computed tomography is required to identify the extent of injury and any involvement of the spinal canal or neural structures. Traumatic spinal fractures are a “red flag” condition, and suspected burst fractures require emergent evaluation and imaging and should always be referred to a spine specialist.
“I Know I Have Fibromyalgia, but My Back Hurts.”: Back Pain and Fibromyalgia
Authors: Standaert Christopher J. , Levy Isaiah
Published: November 2024

Low back pain (LBP) and fibromyalgia coexist in many patients, and the majority of those with fibromyalgia experience LBP. The frequencies of depression, anxiety, post-traumatic stress disorder, and trauma are elevated in the populations of individuals with fibromyalgia and with chronic LBP compared to those without chronic pain. Fibromyalgia is characterized by widespread/multifocal pain, frequently associated with other somatic symptoms like sleep disturbance, fatigue, and cognitive dysfunction. It is increasingly considered a disorder of central sensitization with disturbances of pain processing and regulation. The diagnosis of fibromyalgia is complicated by multiple published criteria and provider reliance on expert or personal opinion. Treating those with the diagnosis of fibromyalgia presenting for care for LBP involves understanding their experiences with the health care system, mindfulness of their experience with chronic pain, and the need to work through an appropriate diagnostic approach to LBP independent of their long-standing pain.
“It Hurt So Much I Had to Come out of the Game.”: A 14-Year-Old Soccer Player with Acute Low Back Pain
Authors: Chowdhary Kuntal , Standaert Christopher J.
Published: November 2024

The most common cause of LBP in an adolescent athlete is a stress fracture of the pars interarticularis of the vertebral arch (isthmic spondylolysis). Spondylolysis can occur gradually or present acutely with low back or upper sacral area pain. Leg pain raises concerns for other conditions, such as a concurrent spondylolisthesis or disc herniation. The rate of asymptomatic pars fractures in adolescent athletes is about 10%, so a diagnosis cannot be made on plain radiographs alone. A combination of magnetic resonance imaging, nuclear imaging, and computed tomography is required. The fundamental treatment of a painful spondylolysis/pars fracture in an adolescent athlete is relative rest. As acute pars fractures have a mean healing time of over 100 days, activity should be restricted for 3 months, followed by comprehensive rehabilitation. Average time to return-to-play is 6–7 months. 85% of affected athletes return to sports, and very few require surgery.
“I’m Only in My Second Trimester, but Now My Back Hurts.”: Back Pain in Pregnancy
Authors: Bitterman Jason S.
Published: November 2024

Most pregnant women experience low back pain (LBP). “Pregnancy-related back pain” is an umbrella term for pregnancy-related low back pain (PLBP) and pelvic girdle pain (PGP). The cause of LBP in pregnancy is generally poorly understood but may be related to hormonal changes resulting in increased joint laxity and postural and muscular changes associated with a gravid uterus. PLBP presents with lower lumbar pain, while the more common PGP presents with posterior pelvic/sacral area pain. True radicular pain or radiculopathy should raise concern for spinal pathology, such as disc herniation. Due to the risks of radiation during pregnancy, radiographs and CT imaging are best avoided in this population. PLBP and PGP are treated nonoperatively with physical therapy, bracing, activity modification, and education. Aquatic therapy, massage, and yoga may be additional options but are not well studied. It is important to follow patients through both their pregnancy and postpartum care.
“I Didn’t Think This Third Pregnancy Was Going to Be So Hard on Me.”: A 33-Year-Old with Postpartum Pelvic Pain
Authors: Marcotte Marissa L. , Kumar Rupali
Published: November 2024

Pain during pregnancy and postpartum is commonly experienced in the posterior pelvic region. This may be related to ligamentous laxity, postural changes, and biomechanical changes or trauma associated with delivery. While low back pain (LBP) is common during pregnancy and in the postpartum period, one should be cautious to not write off the pain as “expected” or “normal,” and thus fail to address it. Rehabilitation can focus on trunk and pelvic exercise, muscle energy techniques, soft tissue mobilization, and stretching. Supportive footwear and a sacroiliac joint stability belt can offer immediate improvement. Postpartum depression can be a confounding factor in those with LBP postpartum and needs to be addressed proactively. Although postpartum use of medications is complicated by the potential for uptake in breast milk, most antidepressants are not strictly contraindicated. Postpartum mothers need support and sleep, both of which may directly affect their rehabilitation/recovery and mood.
“I Want to Stay in My Home.”: An 87-Year-Old with Back Pain, Heart Failure, and Diabetes
Authors: Lawson Laura R. , Kaye Weiner Debra
Published: November 2024

Chronic pain cannot be viewed in one dimension, and older adults are often plagued with other contributors to disability. Multimorbidity, polypharmacy, depression and anxiety, and frailty complicate the care of older patients, who require a thorough, multidimensional evaluation. While older patients with acute low back pain (LBP) warrant urgent clinical evaluation and imaging as concerns of serious pathology are present in older individuals, depression, anxiety, social isolation, and elevated fall risk are concerns in all older adults, especially those with multiple chronic medical issues. As dementia affects over one-third of those over age 85, cognitive evaluation should be included in medical care that addresses the full scope of their physical and psychosocial needs. Pain, physical function, safety at home, maintaining independence, and preventing further frailty are critical goals of care. Treatment with any type of medication, exercise, or home modification requires individual consideration of potential benefit and complications.
Assessing Attention-Deficit/Hyperactivity Disorder in Post-9/11 Veterans: Prevalence, Measurement Correspondence, and Comorbidity With Posttraumatic Stress Disorder
Authors: Knight Arielle R , Kim Sahra , Currao Alyssa , Lebas Adam , Nowak Madeleine K , Milberg William P , Fortier Catherine B
Published: November 2024

Introduction

Attention-deficit/hyperactivity disorder (ADHD) is common among Veterans but overlapping symptoms with other prevalent psychiatric disorders (e.g., posttraumatic stress disorder [PTSD]) complicate diagnosis. This study aims to (1) assess the prevalence of ADHD, (2) evaluate the correspondence between ADHD self-report measures, and (3) examine the association between ADHD and PTSD in a sample of combat-deployed post-9/11 Veterans.

Materials and Methods

A total of 332 combat-deployed post-9/11 Veterans from VA Boston Healthcare System completed the Clinician-Administered PTSD Rating Scale, 2 ADHD self-report questionnaires (Wender Utah Rating Scale–25 and the Adult ADHD Self-Report Scale v1.1), and report of the presence/absence of a historical ADHD diagnosis. Attention-deficit/hyperactivity disorder status via Wender Utah Rating Scale ([WURS-25] criterion standard) was compared to historical ADHD diagnosis and the ASRSv.1.1 screener. Log-binomial regression models assessed the relationship between ADHD and PTSD. This study was reviewed and approved by the VA Boston Institutional Review Board.

Results

In all, 12.7% of the sample met criteria for ADHD per the WURS-25. The WURS-25 demonstrated poor sensitivity with historical ADHD diagnosis (27.7%) but adequate specificity (90.3%). Poor sensitivity (60.7%) and specificity (60.8%) were observed between the WURS-25 and the ASRS-v.1.1. The prevalence of ADHD was 2.5 times as high for Veterans with a history of PTSD (Prevalence Ratio [PR] = 2.53, 95% CI: 1.11, 7.28) and over twice as high for those with current PTSD (PR = 2.19, 95% CI: 1.17, 4.38).

Conclusions

Attention-deficit/hyperactivity disorder is prevalent in this sample of Veterans and is associated with an increased risk of current and lifetime PTSD. The low correspondence across self-report ADHD measures illustrates the complexity of assessing ADHD in this highly comorbid population. When evaluating ADHD in Veterans, clinicians should carefully consider alternative and contributory symptom etiologies, such as PTSD, to ensure accurate diagnosis and treatment.
The diverse star formation histories of early massive, quenched galaxies in modern galaxy formation simulations
Authors: Lagos Claudia del P , Valentino Francesco , Wright Ruby J , de Graaff Anna , Glazebrook Karl , De Lucia Gabriella , Robotham Aaron S G , Nanayakkara Themiya , Chandro-Gomez Angel , Bravo Matías , Baugh Carlton M , Harborne Katherine E , Hirschmann Michaela , Fontanot Fabio , Xie Lizhi , Chittenden Harry
Published: November 2024

We present a comprehensive study of the star formation histories of massive-quenched galaxies at $z=3$ in three semi-analytical models (Shark, gaea, Galform) and three cosmological hydrodynamical simulations (Eagle, IllustrisTNG, Simba). We study the predicted number density and stellar mass function of massive-quenched galaxies, their formation and quenching time-scales and star formation properties of their progenitors. Predictions are disparate in all these diagnostics, for instance: (i) some simulations reproduce the observed number density of very massive-quenched galaxies ($\gt 10^{11}\, \rm {\rm M}_{\odot }$) but underpredict the high density of intermediate-mass ones, while others fit well the lower masses but underpredict the higher ones; (ii) in most simulations, except for gaea and Eagle, most massive-quenched galaxies had starburst periods, with the most intense ones happening at $4\lt z\lt 5$; however, only in Shark and IllustrisTNG we do find a large number of progenitors with star formation rates $\gt 300\rm \, {\rm M}_{\odot }\, yr^{-1}$; (iii) quenching time-scales are in the range $\approx 20\!-\!150$ Myr depending on the simulation; among other differences. These disparate predictions can be tied to the adopted active galactic nucleus (AGN) feedback model. For instance, the explicit black hole (BH) mass dependence to trigger the ‘radio mode’ in IllustrisTNG and Simba makes it difficult to produce quenched galaxies with intermediate stellar masses, also leading to higher baryon collapse efficiencies ($\approx 15\!-\!30$ per cent); while the strong bolometric luminosity dependence of the AGN outflow rate in gaea leads to BHs of modest mass quenching galaxies. Current observations are unable to distinguish between these different predictions due to the small sample sizes. However, these predictions are testable with current facilities and upcoming observations, allowing a ‘true physics experiment’ to be carried out.
Unveiling AGN outflows: [O iii] outflow detection rates and correlation with low-frequency radio emission
Authors: Escott Emmy L , Morabito Leah K , Scholtz Jan , Hickox Ryan C , Harrison Chris M , Alexander David M , Arnaudova Marina I , Smith Daniel J B , Duncan Kenneth J , Petley James , Kondapally Rohit , Calistro Rivera Gabriela , Kolwa Sthabile
Published: November 2024

Some active galactic nuclei (AGN) host outflows which have the potential to alter the host galaxy’s evolution (AGN feedback). These outflows have been linked to enhanced radio emission. Here, we investigate the connection between low-frequency radio emission using the international LOw Frequency ARray (LOFAR) telescope and [O iii] $\lambda$5007 ionized gas outflows using the Sloan Digital Sky Survey. Using the LOFAR Two-metre Sky Survey (LoTSS) Deep Fields, we select 198 AGN with optical spectra, 115 of which are detected at 144 MHz, and investigate their low-frequency radio emission properties. The majority of our sample do not show a radio excess when considering radio luminosity – star formation rate relationship, and are therefore not driven by powerful jets. We extract the [O iii] $\lambda$5007 kinematics and remove AGN luminosity dependencies by matching the radio detected and non-detected AGN in $L_{\mathrm{6\, \mu m}}$ and redshift. Using both spectral fitting and $W_{80}$ measurements, we find radio detected AGN have a higher outflow rate (67.2 $\pm$ 3.4 per cent) than the radio non-detected AGN (44.6 $\pm$ 2.7 per cent), indicating a connection between ionized outflows and the presence of radio emission. For spectra where there are two components of the [O iii] emission line present, we normalize all spectra by the narrow component and find that the average broad component in radio detected AGN is enhanced compared to the radio non-detected AGN. This could be a sign of higher gas content, which is suggestive of a spatial relationship between [O iii] outflows and radio emission in the form of either low-powered jets or shocks from AGN winds.
Star cluster formation from turbulent clumps – IV. Protoplanetary disc evolution
Authors: Gautam Aayush , Farias Juan P , Tan Jonathan C
Published: November 2024

Most stars are born in the crowded environments of gradually forming star clusters. Dynamical interactions between close-passing stars and the evolving ultraviolet radiation fields from proximate massive stars are expected to sculpt the protoplanetary discs (PPDs) in these clusters, potentially contributing to the diversity of planetary systems that we observe. Here, we investigate the impact of cluster environment on disc demographics by implementing simple PPD evolution models within N-body simulations of gradual star cluster formation, containing 50 per cent primordial binaries. We consider a range of star formation efficiency per free-fall time, $\epsilon _{\rm ff}$, and mass surface density of the natal cloud environment, $\Sigma _{\rm cloud}$, both of which affect the overall duration of cluster formation. We track the interaction history of all stars to estimate the dynamical truncation of the discs around stars involved in close encounters. We also track external photoevaporation of the discs due to the ionizing radiation field of the nearby high- and intermediate-mass ($\gt 5\,{\rm M}_\odot$) stars. We find that $\epsilon _{\rm ff}$, $\Sigma _{\rm cloud}$, and the presence of primordial binaries have major influences on the masses and radii of the disc population. In particular, external photoevaporation has a greater impact than dynamical interactions in determining the fate of discs in our clusters.
Limits on dark matter compact objects implied by supermagnified stars in lensing clusters
Authors: Müller Claudi Vall , Miralda-Escudé Jordi
Published: November 2024

Supermagnified stars are gravitationally lensed individual stars that are located close to a caustic of a lensing galaxy cluster, and have their flux magnified by a large enough factor (typically ${\sim} 1000$) to make them detectable with present telescopes. The maximum magnification is limited by microlensing caused by intracluster stars or other compact objects, which create a network of corrugated critical lines with an angular width proportional to the surface density of microlenses. We consider a set of nine cases of supermagnified stars reported in the literature, and derive an upper limit on the surface density of compact objects, such as primordial black holes, that might be present as a fraction of the dark matter in addition to known intracluster stars. Any such additional compact objects would widen the corrugated critical line network and therefore the width of the distribution of supermagnified stars around the modelled critical lines of the lens. We find that any compact objects, including primordial black holes, with masses above ${\sim} 10^{-6} \, {\rm M}_\odot$ (below which the microcaustics are closer together than the typical angular size of supermagnified stars) cannot account for more than ${\sim} 2$ per cent of the dark matter.
Elevated Rates of Molecular Evolution Genome-wide in Mutualist Legumes and Rhizobia
Authors: Harrison Tia L , Stinchcombe John R , Frederickson Megan E
Published: November 2024

Rates of molecular evolution vary greatly among even closely related species. Although theory predicts that antagonistic interactions between species increase rates of molecular evolution, predictions for how mutualism affects evolutionary rates are mixed. We compared rates of molecular evolution between (i) mutualistic and non-mutualistic legumes, (ii) an independent set of symbiotic rhizobia and their non-symbiotic close relatives, and (iii) symbiotic and non-symbiotic clades within Ensifer, a diverse genus of bacteria with various lifestyles. We assembled transcriptomes de novo for 12 legume species and calculated dN/dS ratios at orthologous genes in all species to determine if genes in mutualistic plants evolve faster or slower than in their non-mutualistic relatives. We also calculated dN/dS ratios in genes known to be important for symbiosis. We found that mutualists have higher rates of molecular evolution genome-wide compared to non-mutualistic legumes, but this pattern did not hold in symbiosis genes. We next calculated dN/dS ratios in 14 bacteria species across the proteobacteria phylogeny that differ in whether they associate mutualistically with plants, using published data. In most pairs, symbiotic rhizobia show higher dN/dS values compared to their non-symbiotic relatives. Within a bacterial genus with many well-characterized mutualist species (Ensifer), we calculated dN/dS ratios in symbiotic and non-symbiotic clades and found that symbiotic lineages have higher rates of molecular evolution genome-wide, but not at genes on the symbiotic plasmid pSymB. Our results suggest that although mutualism between legumes and rhizobia is associated with elevated rates of molecular evolution genome-wide, symbiosis genes may be evolutionarily stagnant.
The retinoic acid family-like nuclear receptor SmRAR identified by single-cell transcriptomics of ovarian cells controls oocyte differentiation in Schistosoma mansoni
Authors: Moescheid Max F , Lu Zhigang , Soria Carmen Diaz , Quack Thomas , Puckelwaldt Oliver , Holroyd Nancy , Holzaepfel Pauline , Haeberlein Simone , Rinaldi Gabriel , Berriman Matthew , Grevelding Christoph G
Published: November 2024

Studies on transcription regulation in platyhelminth development are scarce, especially for parasitic flatworms. Here, we employed single-cell transcriptomics to identify genes involved in reproductive development in the trematode model Schistosoma mansoni. This parasite causes schistosomiasis, a major neglected infectious disease affecting >240 million people worldwide. The pathology of schistosomiasis is closely associated with schistosome eggs deposited in host organs including the liver. Unlike other trematodes, schistosomes exhibit distinct sexes, with egg production reliant on the pairing-dependent maturation of female reproductive organs. Despite this significance, the molecular mechanisms underlying ovary development and oocyte differentiation remain largely unexplored. Utilizing an organ isolation approach for S. mansoni, we extracted ovaries of paired females followed by single-cell RNA sequencing (RNA-seq) with disassociated oocytes. A total of 1967 oocytes expressing 7872 genes passed quality control (QC) filtering. Unsupervised clustering revealed four distinct cell clusters: somatic, germ cells and progeny, intermediate and late germ cells. Among distinct marker genes for each cluster, we identified a hitherto uncharacterized transcription factor of the retinoic acid receptor family, SmRAR. Functional analyses of SmRAR and associated genes like Smmeiob (meiosis-specific, oligonucleotide/oligosaccharide binding motif (OB) domain-containing) demonstrated their pairing-dependent and ovary-preferential expression and their decisive roles in oocyte differentiation of S. mansoni.
Comparative molecular dynamics calculations of duplexation of chemically modified analogs of DNA used for antisense applications
Authors: Galindo-Murillo Rodrigo , Cohen Jack S , Akabayov Barak
Published: November 2024

We have subjected several analogs of DNA that have been widely used as antisense oligonucleotide (ASO) inhibitors of gene expression to comparative molecular dynamics (MD) calculations of their ability to form duplexes with DNA and RNA. The analogs included in this study are the phosphorothioate (PS), peptide nucleic acid (PNA), locked nucleic acid (LNA), morpholino nucleic acid (PMO), the 2′-OMe, 2′-F, 2′-methoxyethyl (2′-MOE) and the constrained cET analogs, as well as the natural phosphodiester (PO) as control, for a total of nine structures, in both XNA–DNA and XNA–RNA duplexes. This is intended as an objective criterion for their relative ability to duplex with an RNA complement and their comparative potential for antisense applications. We have found that the constrained furanose ring analogs show increased stability when considering this study’s structural and energetic parameters. The 2′-MOE modification, even though energetically stable, has an elevated dynamic range and breathing properties due to the bulkier moiety in the C2′ position of the furanose. The smaller modifications in the C2′ position, 2′-F, 2′-OMe and PS also form stable and energetically favored duplexes with both DNA and RNA. The morpholino moiety allows for increased tolerance in accommodating either DNA or RNA and the PNA, with the PNA being the most energetically stable, although with a preference for the B-form DNA. In summary, we can rank the overall preference of hybrid strand formations as PNA > cET/LNA > PS/2′-F/2′-OMe > morpholino > 2′-MOE for the efficacy of duplex formation.
Gigantic-oxidative atomic-layer-by-layer epitaxy for artificially designed complex oxides
Authors: Zhou Guangdi , Huang Haoliang , Wang Fengzhe , Wang Heng , Yang Qishuo , Nie Zihao , Lv Wei , Ding Cui , Li Yueying , Lin Jiayi , Yue Changming , Li Danfeng , Sun Yujie , Lin Junhao , Zhang Guang-Ming , Xue Qi-Kun , Chen Zhuoyu
Published: November 2024

In designing material functionalities for transition metal oxides, lattice structure and d-orbital occupancy are key determinants. However, the modulation of these two factors is inherently limited by the need to balance thermodynamic stability, growth kinetics, and stoichiometry precision, particularly for metastable phases. We introduce a methodology, namely the gigantic-oxidative atomic-layer-by-layer epitaxy (GOALL-Epitaxy), enhancing oxidation power 3-4 orders of magnitude beyond conventional pulsed laser deposition (PLD) and oxide molecular beam epitaxy (OMBE), while ensuring atomic-layer-by-layer growth of designed complex structures. Thermodynamic stability is markedly augmented with stronger oxidation at elevated temperatures, whereas growth kinetics is sustained by laser ablation at lower temperatures. We demonstrate the accurate growth of complex nickelates and cuprates, especially an artificially designed structure with alternating single and double NiO2 layers possessing distinct nominal d-orbital occupancy, as a parent of high-temperature superconductor. The GOALL-Epitaxy enables material discovery within the vastly broadened growth parameter space.