bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

SUMMARY
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.