bluuebunny/crossref_metadata_2025_split huggingface dataset:
The fission yeast methyl phosphate capping enzyme Bmc1 guides 2′-O-methylation of the U6 snRNA
Authors: Porat Jennifer , Slat Viktor A , Rader Stephen D , Bayfield Mark A 
Published: July 2023

Abstract
Splicing requires the tight coordination of dynamic spliceosomal RNAs and proteins. U6 is the only spliceosomal RNA transcribed by RNA Polymerase III and undergoes an extensive maturation process. In humans and fission yeast, this includes addition of a 5′ γ-monomethyl phosphate cap by members of the Bin3/MePCE family as well as snoRNA guided 2′-O-methylation. Previously, we have shown that the Bin3/MePCE homolog Bmc1 is recruited to the S. pombe telomerase holoenzyme by the LARP7 family protein Pof8, where it acts in a catalytic-independent manner to protect the telomerase RNA and facilitate holoenzyme assembly. Here, we show that Bmc1 and Pof8 are required for the formation of a distinct U6 snRNP that promotes 2′-O-methylation of U6, and identify a non-canonical snoRNA that guides this methylation. We also show that the 5′ γ-monomethyl phosphate capping activity of Bmc1 is not required for its role in promoting snoRNA guided 2′-O-methylation, and that this role relies on different regions of Pof8 from those required for Pof8 function in telomerase. Our results are consistent with a novel role for Bmc1/MePCE family members in stimulating 2′-O-methylation and a more general role for Bmc1 and Pof8 in guiding noncoding RNP assembly beyond the telomerase RNP.
Physicians’ Hierarchy of Tumor Biomarkers for Optimizing Chemotherapy in Breast Cancer Care
Authors: Thannickal Halle H , Eltoum Noon , Henderson Nicole L , Wallner Lauren P , Wagner Lynne I , Wolff Antonio C , Rocque Gabrielle B 
Published: July 2023

Abstract

Background
Tumor biomarkers are regularly used to guide breast cancer treatment and clinical trial enrollment. However, there remains a lack of knowledge regarding physicians’ perspectives towards biomarkers and their role in treatment optimization, where treatment intensity is reduced to minimize toxicity.

Methods
Thirty-nine academic and community oncologists participated in semi-structured qualitative interviews, providing perspectives on optimization approaches to chemotherapy treatment. Interviews were audio-recorded, transcribed, and analyzed by 2 independent coders utilizing a constant comparative method in NVivo. Major themes and exemplary quotes were extracted. A framework outlining physicians’ conception of biomarkers, and their comfortability with their use in treatment optimization, was developed.

Results
In the hierarchal model of biomarkers, level 1 is comprised of standard-of-care (SoC) biomarkers, defined by a strong level of evidence, alignment with national guidelines, and widespread utilization. Level 2 includes SoC biomarkers used in alternative contexts, in which physicians expressed confidence, yet less certainty, due to a lack of data in certain subgroups. Level 3, or experimental, biomarkers created the most diverse concerns related to quality and quantity of evidence, with several additional modulators.

Conclusion
This study demonstrates that physicians conceptualize the use of biomarkers for treatment optimization in successive levels. This hierarchy can be used to guide trialists in the development of novel biomarkers and design of future trials.
CHROMATIN REMODELING 11-dependent nucleosome occupancy affects disease resistance in rice
Authors: Liu He , Li Jing , Wang Shuai , Hua Jian , Zou Baohong 
Published: July 2023

Abstract
Plant immune responses involve transcriptional reprograming of defense response genes, and chromatin remodeling is important for transcriptional regulation. However, nucleosome dynamics induced by pathogen infection and its association with gene transcription are largely unexplored in plants. Here, we investigated the role of the rice (Oryza sativa) gene CHROMATIN REMODELING 11 (OsCHR11) in nucleosome dynamics and disease resistance. Nucleosome profiling revealed that OsCHR11 is required for the maintaining of genome-wide nucleosome occupancy in rice. Nucleosome occupancy of 14% of the genome was regulated by OsCHR11. Infection of bacterial leaf blight Xoo (Xanthomonas oryzae pv. oryzae) repressed genome-wide nucleosome occupancy, and this process depended on OsCHR11 function. Furthermore, OsCHR11/Xoo-dependent chromatin accessibility correlated with gene transcript induction by Xoo. In addition, accompanied by increased resistance to Xoo, several defense response genes were differentially expressed in oschr11 after Xoo infection. Overall, this study reports the genome-wide effects of pathogen infection on nucleosome occupancy, its regulation, and its contribution to disease resistance in rice.
Associations of smartphone usage patterns with sleep and mental health symptoms in a clinical cohort receiving virtual behavioral medicine care: a retrospective study
Authors: Knights Jonathan , Shen Jacob , Mysliwiec Vincent , DuBois Holly 
Published: July 2023

Abstract

Study Objectives
We sought to develop behavioral sleep measures from passively sensed human-smartphone interactions and retrospectively evaluate their associations with sleep disturbance, anxiety, and depressive symptoms in a large cohort of real-world patients receiving virtual behavioral medicine care.

Methods
Behavioral sleep measures from smartphone data were developed: daily longest period of smartphone inactivity (inferred sleep period [ISP]); 30-day expected period of inactivity (expected sleep period [ESP]); regularity of the daily ISP compared to the ESP (overlap percentage); and smartphone usage during inferred sleep (disruptions, wakefulness during sleep period). These measures were compared to symptoms of sleep disturbance, anxiety, and depression using linear mixed-effects modeling. More than 2300 patients receiving standard-of-care virtual mental healthcare across more than 111 000 days were retrospectively analyzed.

Results
Mean ESP duration was 8.4 h (SD = 2.3), overlap percentage 75% (SD = 18%) and disrupted time windows 4.85 (SD = 3). There were significant associations between overlap percentage (p &lt; 0.001) and disruptions (p &lt; 0.001) with sleep disturbance symptoms after accounting for demographics. Overlap percentage and disruptions were similarly associated with anxiety and depression symptoms (all p &lt; 0.001).

Conclusions
Smartphone behavioral measures appear useful to longitudinally monitor sleep and benchmark depressive and anxiety symptoms in patients receiving virtual behavioral medicine care. Patterns consistent with better sleep practices (i.e. greater regularity of ISP, fewer disruptions) were associated with lower levels of reported sleep disturbances, anxiety, and depression.
Elevated nutrient supply can exert worse effects on Norway spruce than drought, viewed through chemical defence against needle rust
Authors: Ganthaler Andrea , Guggenberger Andreas , Stöggl Wolfgang , Kranner Ilse , Mayr Stefan 
Published: July 2023

Abstract

Abiotic factors such as water and nutrient availability can exert a dominant influence on the susceptibility of plants to various pathogens. Effects of abiotic environmental factors on phenolic compound concentrations in the plant tissue may represent one of the major underlying mechanisms, as these compounds are known to play a substantial role in plant resistance to pests. In particular, this applies to conifer trees, in which a large range of phenolic compounds are produced constitutively and/or induced by pathogen attack. We subjected Norway spruce saplings to water limitation and elevated nutrient supply over 2 years and subsequently controlled infection with the needle rust Chrysomyxa rhododendri (DC.) de Bary and analysed both constitutive and inducible phenolic compound concentrations in the needles as well as the degree of infection. Compared with the control group, both drought and fertilization profoundly modified the constitutive and pathogen-induced profiles of phenolic compounds, but had little impact on the total phenolic content. Fertilization predominantly affected the inducible phenolic response and led to higher infection rates by C. rhododendri. Drought stress, in contrast, mainly shaped the phenolic profiles in healthy plant parts and had no consequences on the plant susceptibility. The results show that specific abiotic effects on individual compounds seem to be decisive for the infection success of C. rhododendri, whereby the impaired induced response in saplings subjected to nutrient supplementation was most critical. Although drought effects were minor, they varied depending on the time and length of water limitation. The results indicate that prolonged drought periods in the future may not significantly alter the foliar defence of Norway spruce against C. rhododendri, but fertilization, often propagated to increase tree growth and forest productivity, can be counterproductive in areas with high pathogen pressure.

Highlights
Lean Health Care Internships: A Novel Systems-Based Practice Education Program for Undergraduate Medical Students
Authors: Erdmann Marjorie A. , Paramel Ipe S. , Marshall Carolyn M. 
Published: July 2023

Abstract

Problem
Given the United States’ urgency for systemic-level improvements to care, advancing systems-based practice (SBP) competency among future physicians is crucial. However, SBP education is inadequate, lacks a unifying framework and faculty confidence in its teaching, and is taught late in the medical education journey.

Approach
The Oklahoma State University Center for Health Systems Innovation (CHSI) created an SBP program relying on Lean Health Care for a framework and targeted medical students before their second year began. Lean curricula were developed (lecture and simulation) and a partnership with a hospital was secured for work-based practice. The CHSI developed a skills assessment tool for preliminary evaluation of the program. In June 2022, 9 undergraduate medical students responded to a Lean Health Care Internship (LHCI) presentation.

Outcomes
Student SBP skills increased after training and again after work-based practice. All 9 students reported that their conceptualization of problems in health care changed “extraordinarily,” and they were “extraordinarily” confident in their ability to approach another health care problem by applying the Lean method. The LHCI fostered an awareness of physicians as interdependent systems citizens, a key goal of SBP competency. After the internship concluded, the Lean team recommendations generated a resident-led quality assurance performance improvement initiative for bed throughput.

Next Steps
The LHCI was effective in engaging students and building SBP skills among undergraduate medical education students. The levels of student enthusiasm and skill acquisition exceeded the Lean trainers’ expectations. The researchers will continue to measure LHCI’s effect on students’ rotation experiences to better evaluate the long-term benefit of introducing SBP concepts earlier in medical education. The program’s success has spurred enthusiasm for continued collaboration with hospital and residency programs. Program administrators are exploring how to broaden access.
Testosterone Therapy Is Associated With Increased Odds of Quadriceps Tendon Injury
Authors: Meghani Ozair , Albright J. Alex , Testa Edward J. , Arcand Michel A. , Daniels Alan H. , Owens Brett D. 
Published: July 2023

Abstract

Background
Anabolic steroid use at supraphysiologic doses has been associated with an increased risk of tendon injury. However, the musculoskeletal effects of testosterone therapy in the clinical setting are not well understood.

Questions/purposes
(1) Is prescription testosterone associated with a higher odds of subsequent quadriceps muscle or tendon injury? (2) Is prescription testosterone associated with a higher odds of surgical repair of the quadriceps tendon?

Methods
The PearlDiver Database, which contains data on Medicaid, Medicare, and commercially insured patients, allows for a large representative sample of the US population including both publicly and privately insured patients. The database was queried for all patients between 2011 and 2018 who filled a testosterone prescription. Additionally, all quadriceps injuries using ICD-9 and ICD-10 codes between 2011 and 2018 were queried. Propensity score matching based on age, sex, Charlson comorbidity index, and specific comorbidities allowed us to create matched control groups. We used the t-test and chi-square analysis to compare the unmatched and matched cohorts. A total of 151,797 patients (123,627 male patients and 28,170 female patients) with a history of filled testosterone prescriptions were included in the study after matching with the control group, which was of equal size and representation of age, male-female proportions, and comorbidities. Chi-square and logistic regression analyses were performed to compare odds of quadriceps injury and quadriceps tendon repair among the testosterone groups to that of their respective control groups by age and sex.

Results
Within 1 year of filling prescriptions for testosterone, 0.06% (97 of 151,797) of patients experienced a quadriceps injury compared with less than 0.01% (18 of 151,797) of patients in the control group (OR 5.4 [95% CI 3.4 to 9.2]; p < 0.001). Within the sex-specific matched groups, filling a testosterone prescription was associated with an increase in the odds of quadriceps injury in male patients within 1 year of the prescription (OR 5.8 [95% CI 3.5 to 10.3]; p < 0.001). Additionally, patients who filled a testosterone prescription were at increased risk of having quadriceps tendon repair within a year of the injury than were patients in the matched control group (OR 4.7 [95% CI 2.0 to 13.8]; p = 0.001).

Conclusion
Considering these findings, it is important for physicians to counsel patients receiving testosterone replacement therapy of the substantially increased odds of quadriceps tendon injury. Future investigations into the mechanisms of influence of exogenous anabolic steroids on tendon injury remains of interest.

Level of Evidence
Level III, therapeutic study.
Improvement of Global Longitudinal Strain and Myocardial Work in Type 2 Diabetes Patients on Sodium–Glucose Cotransporter 2 Inhibitors Therapy
Authors: Russo Vincenzo , Malvezzi Caracciolo D'Aquino Marco , Caturano Alfredo , Scognamiglio Gabriella , Pezzullo Enrica , Fabiani Dario , Del Giudice Carmen , Carbone Andreina , Bottino Roberta , Caso Valentina , Nigro Gerardo , Golino Paolo , Liccardo Biagio , D'Andrea Antonello 
Published: July 2023

Abstract:
Sodium–glucose cotransporter 2 inhibitors (SGLT2-i) are a novel class of oral hypoglycemic agents currently used among patients with type 2 diabetes mellitus (T2DM). The effects of SGLT2-i inhibitors on cardiac structure and function are not fully understood. The aim of this study is to evaluate the echocardiographic changing among patients with well-controlled T2DM treated with SGLT2-i in real-world setting. Thirty-five well-controlled T2DM patients (65 ± 9 years, 43.7% male) with preserved left ventricular ejection fraction (LVEF) and 35 age and sex-matched controls were included. T2DM patients underwent clinical and laboratory evaluation; 12-lead surface electrocardiogram; 2-dimensional color Doppler echocardiography at enrolment, before SGLT2-i administration, and at 6 months follow-up after an uninterrupted 10 mg once daily of empagliflozin (n: 21) or dapagliflozin (n: 14). Standard echocardiographic measurements, LV global longitudinal strain (LV-GLS), global wasted work, and global work efficiency were calculated. T2DM patients showed higher E\E′ ratio (8.3 ± 2.5 vs. 6.3 ± 0.9; P < 0.0001) and lower LV-GLS (15.8 ± 8.1 vs. 22.1 ± 1.4%; P < 0.0001) and global myocardial work efficiency (91 ± 4 vs. 94 ± 3%; P: 0.0007) compared with age and sex-matched controls. At 6-month follow-up, T2DM patients showed a significant increase in LVEF (58.9 ± 3.2 vs. 62 ± 3.2; P < 0.0001), LV-GLS (16.2 ± 2.8 vs. 18.7 ± 2.4%; P = 0.003), and global work efficiency (90.3 ± 3.5 vs. 93.3 ± 3.2%; P = 0.0004) values; conversely, global wasted work values (161.2 ± 33.6 vs. 112.72 ± 37.3 mm Hg%; P < 0.0001) significantly decreased. Well-controlled T2DM patients with preserved LVEF who are treated with a SGLT2-i on top of the guidelines direct medical therapy showed a favorable cardiac remodeling, characterized by the improvement of LV-GLS and myocardial work efficiency.
Economic and Clinical Outcomes of Pediatric Patients Under Two With Respiratory Syncytial Virus Infection in Thailand: A Real-world Retrospective Cohort Study
Authors: Tan Chia Jie , Patikorn Chanthawat , Techasaensiri Chonnamet , Pattanaprateep Oraluck , Chaiyakunapruk Nathorn 
Published: July 2023

Background:
Respiratory syncytial virus (RSV) is a common cause of acute respiratory tract infection in children, including in Thailand. We conducted this study to evaluate the economic and clinical outcomes of patients <2 years old with RSV infection at a tertiary teaching hospital in Thailand.

Methods:
This was a retrospective cohort study during 2014–2021. To be eligible, patients had to report at least 1 positive RSV test and were <2 years old. Descriptive statistics were used to describe baseline characteristics, healthcare resource utilization, direct medical costs (1 US dollars [USD] = 31.98 Thai Baht) and clinical outcomes.

Results:
Among 1370 RSV-positive patients, 49.9% of the patients (n = 683) were hospitalized at or within 3 days of RSV diagnosis with a median length of stay of 6 days (interquartile range [IQR]: 4–9 days), 38.8% were diagnosed with RSV-related respiratory complications (n = 532) and 1.5% died during the hospitalization episode (n = 20). A total of 22.5% of hospitalized patients (n = 154) received critical care during the hospitalization episode. The median cost of each RSV episode was USD539 (IQR: USD167–USD2106) and was higher among hospitalized patients (median: USD2112; IQR: USD1379–USD3182) compared with nonhospitalized patients (median: USD167; IQR: USD112–USD276).

Conclusions:
RSV infection represents a potentially important contributor to healthcare resource use and medical costs among children <2 years old in Thailand. Coupled with epidemiologic data, findings from our study will be useful to illustrate the overall economic burden associated with RSV infection among children in Thailand.
Accessory Muscles Associated With the Levator Palpebrae Superioris Muscle in 100 Cadavers
Authors: Nteli Chatzioglou Gkionoul , Kale Ayşin , Özbilen Kemal Turgay , Önal Vildan , Coşkun Osman , Gayretli Özcan 
Published: July 2023

Purpose:
This study aimed to determine the variations of the levator palpebrae superioris muscle and to reveal its morphological features.

Methods:
This study conducted on 100 adult orbit cadavers in the Department of Anatomy, Istanbul University, used an exploratory, descriptive research design. The anatomical and morphological variations of the levator palpebrae superioris muscle and its relationship with the superior ophthalmic vein were evaluated.

Results:
Variations of levator palpebrae superioris muscle were discovered in 11 of 100 orbits. Single (9%), double (1%), and triple (1%) accessory muscle slips were observed. The origin of accessory muscle slips showed variation as the accessory muscle slips originated either from the proximal or distal half of the levator palpebrae superioris muscle. Also, the insertions of accessory muscle slips were variable, as they were inserted into levator aponeurosis, trochlea, lacrimal gland, lateral orbital wall, or the fascia of the superior ophthalmic vein.

Conclusions:
Accessory muscles associated with levator aponeurosis were found in a significant proportion of cadavers. These muscles may cause confusion in orbital surgery and should be taken into account during surgical planning and orientation in the superior orbit.
Chronic Traumatic Encephalopathy in Soccer Players: Review of 14 Cases
Authors: Hageman Gerard , Hageman Ivar , Nihom Jik 
Published: July 2023

Objective:Exposure to repetitive sports-related concussions or (sub)concussive head trauma may lead to chronic traumatic encephalopathy (CTE). Which impact (heading or concussion) poses the greatest risk of CTE development in soccer players?Design:Narrative review.Setting:Teaching hospital and University of Applied sciences.Patients:A literature search (PubMed) was conducted for neuropathologic studies in the period 2005-December 2022, investigating soccer players with dementia and a CTE diagnosis, limited to English language publications. 210 papers were selected for final inclusion, of which 7 papers described 14 soccer players.Assessment:Magnetic resonance imaging studies in soccer players show that lifetime estimates of heading numbers are inversely correlated with cortical thickness, grey matter volume, and density of the anterior temporal cortex. Using diffusion tensor imaging–magnetic resonance imaging, higher frequency of headings—particularly with rotational accelerations—are associated with impaired white matter integrity. Serum neurofilament light protein is elevated after heading.Main Outcome Measures:Chronic traumatic encephalopathy pathology, history of concussion, heading frequency.Results:In 10 of 14 soccer players, CTE was the primary diagnosis. In 4 cases, other dementia types formed the primary diagnosis and CTE pathology was a concomitant finding. Remarkably, 6 of the 14 cases had no history of concussion, suggesting that frequent heading may be a risk for CTE in patients without symptomatic concussion. Rule changes in heading duels, management of concussion during the game, and limiting the number of high force headers during training are discussed.Conclusions:Data suggest that heading frequency and concussions are associated with higher risk of developing CTE in (retired) soccer players. However based on this review of only 14 players, questions persist as to whether or not heading is a risk factor for CTE or long-term cognitive decline.
Exhaled breath analysis in interstitial lung disease
Authors: van der Sar Iris G. , Wijsenbeek Marlies S. , Moor Catharina C. 
Published: July 2023

Purpose of reviewThere is a need for better noninvasive tools to diagnose interstitial lung disease (ILD) and predict disease course. Volatile organic compounds present in exhaled breath contain valuable information on a person's health and may be a novel biomarker in ILD. In this review, we will give an overview of the basic principles of breath analysis, summarize the available evidence in ILD, and discuss future perspectives.Recent findingsAn increasing number of studies on exhaled breath analysis were performed over the last decade in patients with ILD, using two methods for exhaled breath analysis: gas chromatography-mass spectrometry and electronic nose technology. Most studies showed high accuracy for diagnosis of ILD, but study design and methods widely varied. Studies investigating the potential of electronic nose technology to predict treatment response and disease behavior are ongoing.SummaryThe majority of studies using exhaled breath analysis in ILD show promising results for diagnostic purposes, but validation studies are lacking. Larger prospective longitudinal studies using standardized methods are needed to collect the evidence required for developing an approved diagnostic medical test.