bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cysteine post‐translational modifications regulate protein interactions of caveolin‐3
Authors: Ashford Fiona , Kuo Chien‐Wen , Dunning Emma , Brown Elaine , Calagan Sarah , Jayasinghe Izzy , Henderson Colin , Fuller William , Wypijewski Krzysztof 
Published: March 2024

AbstractCaveolae are small flask‐shaped invaginations of the surface membrane which are proposed to recruit and co‐localize signaling molecules. The distinctive caveolar shape is achieved by the oligomeric structural protein caveolin, of which three isoforms exist. Aside from the finding that caveolin‐3 is specifically expressed in muscle, functional differences between the caveolin isoforms have not been rigorously investigated. Caveolin‐3 is relatively cysteine‐rich compared to caveolins 1 and 2, so we investigated its cysteine post‐translational modifications. We find that caveolin‐3 is palmitoylated at 6 cysteines and becomes glutathiolated following redox stress. We map the caveolin‐3 palmitoylation sites to a cluster of cysteines in its C terminal membrane domain, and the glutathiolation site to an N terminal cysteine close to the region of caveolin‐3 proposed to engage in protein interactions. Glutathiolation abolishes caveolin‐3 interaction with heterotrimeric G protein alpha subunits. Our results indicate that a caveolin‐3 oligomer contains up to 66 palmitates, compared to up to 33 for caveolin‐1. The additional palmitoylation sites in caveolin‐3 therefore provide a mechanistic basis by which caveolae in smooth and striated muscle can possess unique phospholipid and protein cargoes. These unique adaptations of the muscle‐specific caveolin isoform have important implications for caveolar assembly and signaling.
Long-term Survival after Volatile or Propofol General Anesthesia for Bladder Cancer Surgery: A Retrospective National Registry Cohort Study
Authors: Enlund Mats , Hållberg Hampus , Berglund Anders , Sherif Amir , Enlund Anna , Bergkvist Leif 
Published: March 2024

Background
Prospective interventional trials and retrospective observational analyses provide conflicting evidence regarding the relationship between propofol versus inhaled volatile general anesthesia and long-term survival after cancer surgery. Specifically, bladder cancer surgery lacks prospective clinical trial evidence.

Methods
Data on bladder cancer surgery performed under general anesthesia between 2014 and 2021 from the National Quality Registry for Urinary Tract and Bladder Cancer and the Swedish Perioperative Registry were record-linked. Overall survival was compared between patients receiving propofol or inhaled volatile for anesthesia maintenance. The minimum clinically important difference was defined as a 5–percentage point difference in 5-yr survival.

Results
Of 7,571 subjects, 4,519 (59.7%) received an inhaled volatile anesthetic, and 3,052 (40.3%) received propofol for general anesthesia maintenance. The two groups were quite similar in most respects but differed in American Society of Anesthesiologists Physical Status and tumor stage. Propensity score matching was used to address treatment bias. Survival did not differ during follow-up (median, 45 months [interquartile range, 33 to 62 months]) in the full unmatched cohort nor after 1:1 propensity score matching (3,052 matched pairs). The Kaplan–Meier adjusted 5-yr survival rates in the matched cohort were 898 of 3,052, 67.5% (65.6 to 69.3%) for propofol and 852 of 3,052, 68.5% (66.7 to 70.4%) for inhaled volatile general anesthesia, respectively (hazard ratio, 1.05 [95% CI, 0.96 to 1.15]; P = 0.332). A sensitivity analysis restricted to 1,766 propensity score–matched pairs of patients who received only one general anesthetic during the study period did not demonstrate a difference in survival; Kaplan–Meier adjusted 5-yr survival rates were 521 of 1,766, 67.1% (64.7 to 69.7%) and 482 of 1,766, 68.9% (66.5 to 71.4%) for propofol and inhaled volatile general anesthesia, respectively (hazard ratio, 1.09 [95% CI, 0.97 to 1.23]; P = 0.139).

Conclusions
Among patients undergoing bladder cancer surgery under general anesthesia, there was no statistically significant difference in long-term overall survival associated with the choice of propofol or an inhaled volatile maintenance.

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Alternate Electrode Placements to Facilitate Frontal Electroencephalography Monitoring in Anesthetized and Critically Ill Patients
Authors: Isik Oliver G. , Chauhan Vikas , Ahmed Meah T. , Chang Brian A. , Cassim Tuan Z. , Graves Morgan C. , Rajan Shobana , Garcia Paul S. 
Published: March 2024

Background:
Frontal electroencephalography (EEG) monitoring can be useful in guiding the titration of anesthetics, but it is not always feasible to place electrodes in the standard configuration in some circumstances, including during neurosurgery. This study compares 5 alternate configurations of the Masimo Sedline Sensor.

Methods:
Ten stably sedated patients in the intensive care unit were recruited. Frontal EEG was monitored in the standard configuration (bifrontal upright) and 5 alternate configurations: bifrontal inverse, infraorbital, lateral upright, lateral inverse, and semilateral. Average power spectral densities (PSDs) with 95% CIs in the alternate configurations were compared to PSDs in the standard configuration. Two-one-sided-testing with Wilcoxon signed-rank tests assessed equivalence in the spectral edge frequency (SEF-95), EEG power, and relative delta (0.5 to 3.5 Hz), alpha (8 to 12 Hz), and beta (20 to 30 Hz) power between each alternate and standard configurations.

Results:
After the removal of unanalyzable tracings, 7 patients were included for analysis in the infraorbital configuration and 9 in all other configurations. In the lateral upright and lateral inverse configurations, PSDs significantly differed from the standard configuration within the 15 to 20 Hz band. The greatest decrease in EEG power was in the lateral inverse configuration (median: −97 dB; IQR: −130, −62 dB). The largest change in frequency distribution of EEG power was in the infraorbital configuration; median SEF-95 change of −1.4 Hz (IQR: −2.8, 0.7 Hz), median relative delta power change of +7.3% (IQR: 1.4%, 7.9%), and median relative alpha power change of −0.6% (IQR: −5.7%, 0.0%).

Conclusions:
These 5 alternate Sedline electrode configurations are suitable options for monitoring frontal EEG when the standard configuration is not possible.
Location, location, location: How does residency program leadership vary according to geographic region?
Authors: Huyke-Hernández Fernando A. , Doxey Stephen A. , Qian Lily J. , Heare Austin , Cunningham Brian P. 
Published: March 2024

Background:
Faculty relationships are key to resident education. Residency applicants may find it more appealing to choose programs where the faculty have a similar background. With the addition of geographic preferences to the application process, applicants may find it beneficial to know general faculty makeup in each region. The purpose of this study was to evaluate the relationship of geographic location and orthopaedic residency leadership characteristics.

Methods:
The Accreditation Council for Graduate Medical Education (ACGME) and Doximity websites were queried in September 2022 to identify United States orthopaedic residency programs for the 2022-2023 cycle. Program attributes were categorized by region. Program leaders evaluated in this study consisted of Chairs, Vice Chairs, Program Directors (PDs), and Assistant PDs.

Results:
A total of 192 programs with 425 leaders were included. Leaders were mostly PDs (42.6%, n=181), men (88.7%, n=377), MDs (90.6%, n=385), and trained in the US (96.9%, n=412). The Northeast had the most programs (n=59, 30.7%) and leadership positions (n=136, 32.0%). The West had higher proportions of internationally-trained and women leaders (8.2%, P=0.046 and 18.0%, P=0.072), although the latter only trended towards significance. The South contained the lowest prevalence of internationally-trained leaders (0.8%, P=0.046). The Midwest exhibited the largest amount of DO leadership (16.0%, P=0.022). The Northeast had more surgeons subspecialized in hand/upper extremity (19.9% vs. 10.0%, P=0.033) yet relatively fewer in oncology (2.9% vs. 10.7%, P=0.041).

Conclusions:
Program attributes varied by region. This information is valuable to applicants and leaders as the field strives to strengthen and diversify its leadership.
Precision dosing for patients on tricyclic antidepressants
Authors: Nakad Zahi , Saab Yolande 
Published: March 2024

Objective
We aim to develop a personalized dosing tool for tricyclic antidepressants (TCAs) that integrates CYP2D6 and CYP2C19 gene variants and their effects while also considering the polypharmacy effect.

Methods
The study first adopted a scoring system that assigns weights to each genetic variant. A formula was then developed to compute the effect of both genes’ variants on drug dosing. The output of the formula was assessed by a comparison with the clinical pharmacogenetics implementation consortium recommendation. The study also accounts for the effect of the co-administration of inhibitors and inducers on drug metabolism. Accordingly, a user-friendly tool, Clinical Dosing Tool ver.2, was created to assist clinicians in dosing patients on TCAs.

Results
The study provides a comprehensive list of all alleles with corresponding activity values and phenotypes for both enzymes. The tool calculated an updated area under the curve ratio that utilizes the effects of both enzymes’ variants for dose adjustment. The tool provided a more accurate individualized dosing that also integrates the polypharmacy effect.

Conclusion
To the best of our knowledge, the literature misses such a tool that provides a numerical adjusted dose based on continuous numerical activity scores for the considered patients’ alleles and phenoconversion.
Associations of ADH1B and ALDH2 genotypes and alcohol flushing with drinking history, withdrawal symptoms, and ICD-10 criteria in Japanese alcohol-dependent men
Authors: Yokoyama Akira , Yokoyama Tetsuji , Yumoto Yosuke , Takimura Tsuyoshi , Toyama Tomomi , Yoneda Junichi , Nishimura Kotaro , Minobe Ruriko , Matsuzaki Takanobu , Kimura Mitsuru , Matsushita Sachio 
Published: March 2024

Objectives
Given the high prevalence of fast-metabolizing alcohol dehydrogenase-1B*2 (ADH1B*2) and inactive aldehyde dehydrogenase-2*2 (ALDH2*2) alleles in East Asians, we evaluated how the ADH1B/ALDH2 genotypes and alcohol flushing might affect the development of alcohol dependence (AD).

Methods
We evaluated how the ADH1B/ALDH2 genotypes and self-reported alcohol flushing affected history of drinking events and withdrawal symptoms and ICD-10 criteria in 4116 Japanese AD men.

Results
The ADH1B*1/*1 group and ALDH2*1/*1 group were 1–5 years younger than the ADH1B*2(+) and ALDH2*1/*2 groups, respectively, for all of the ages at onset of habitual drinking, blackouts, daytime drinking, uncontrolled drinking, withdrawal symptoms, and first treatment for AD, and the current age. Blackouts were more common in the ADH1B*1/*1 group and ALDH2*1/*1 group. Daytime drinking, uncontrolled drinking, and withdrawal symptoms, such as hand tremor, sweating, convulsions, and delirium tremens/hallucinations were more common in the ADH1B*1/*1 group. The ADH1B*1/*1 was positively associated with the ICD-10 criteria for ‘tolerance’ and ‘withdrawal symptoms’. The ADH1B*1/*1 group and ALDH2*1/*2 group had a larger ICD-10 score. Never flushing was reported by 91.7% and 35.2% of the ALDH2*1/*1 and ALDH2*1/*2 carriers, respectively. After a 1–2-year delay in the onset of habitual drinking in the former-/current-flushing group, no differences in the ages of the aforementioned drinking milestones were found according to the flushing status.

Conclusion
The ADH1B*1/*1 and ALDH2*1/*1 accelerated the development of drinking events and withdrawal symptoms in Japanese AD patients. ICD-10 score was larger in the ADH1B*1/*1 group and ALDH2*1/*2 group. The effects of alcohol flushing on drinking events were limited.
Inhibition of sodium-glucose cotransporter-2 and liver-related complications in individuals with diabetes: a Mendelian randomization and population-based cohort study
Authors: Chung Sung Won , Moon Hye-Sung , Shin Hyunjae , Han Hyein , Park Sehoon , Cho Heejin , Park Jeayeon , Hur Moon Haeng , Park Min Kyung , Won Sung-Ho , Lee Yun Bin , Cho Eun Ju , Yu Su Jong , Kim Dong Ki , Yoon Jung-Hwan , Lee Jeong-Hoon , Kim Yoon Jun 
Published: March 2024

Background and Aims:
No medication has been found to reduce liver-related events. We evaluated the effect of sodium-glucose cotransporter-2 inhibitor (SGLT2i) on liver-related outcomes.

Approach and Results:
Single nucleotide polymorphisms associated with SGLT2 inhibition were identified, and a genetic risk score (GRS) was computed using the UK Biobank data (n=337,138). Two-sample Mendelian randomization (MR) was conducted using the FinnGen (n=218,792) database and the UK Biobank data. In parallel, a nationwide population-based study using the Korean National Health Insurance Service (NHIS) database was conducted. The development of liver-related complications (ie, hepatic decompensation, HCC, liver transplantation, and death) was compared between individuals with type 2 diabetes mellitus and steatotic liver diseases treated with SGLT2i (n=13,208) and propensity score–matched individuals treated with dipeptidyl peptidase-4 inhibitor (n=70,342). After computing GRS with 6 single nucleotide polymorphisms (rs4488457, rs80577326, rs11865835, rs9930811, rs34497199, and rs35445454), GRS-based MR showed that SGLT2 inhibition (per 1 SD increase of GRS, 0.1% lowering of HbA1c) was negatively associated with cirrhosis development (adjusted odds ratio=0.83, 95% CI=0.70–0.98, p=0.03) and this was consistent in the 2-sample MR (OR=0.73, 95% CI=0.60–0.90, p=0.003). In the Korean NHIS database, the risk of liver-related complications was significantly lower in the SGLT2i group than in the dipeptidyl peptidase-4 inhibitor group (adjusted hazard ratio=0.88, 95% CI=0.79–0.97, p=0.01), and this difference remained significant (adjusted hazard ratio=0.72–0.89, all p<0.05) across various sensitivity analyses.

Conclusions:
Both MRs using 2 European cohorts and a Korean nationwide population-based cohort study suggest that SGLT2 inhibition is associated with a lower risk of liver-related events.
Cognitive Behavioral Therapy for Insomnia Improves Sleep Outcomes in Individuals With Concussion: A Preliminary Randomized Wait-List Control Study
Authors: Ludwig Rebecca , Rippee Michael , D’Silva Linda , Radel Jeff , Eakman Aaron M. , Beltramo Alvin , Drerup Michelle , Siengsukon Catherine 
Published: March 2024

Objective:
Cognitive behavioral therapy for insomnia (CBT-I) is the gold standard treatment for insomnia, but there is limited evidence on the treatment effect of CBT-I in individuals after a concussion. Therefore, the main purpose of this study was to evaluate the treatment effect of CBT-I on sleep outcomes and postconcussion symptoms.

Setting:
This study was conducted at an academic institution. The CBT-I sessions were conducted using a teleconferencing system (Zoom).

Participants:
Participants were eligible to participate if they were at least 4 weeks post- concussion, aged 18 to 64 years, and scored 10 or more on the Insomnia Severity Index. A total of 40 people were enrolled; 32 participants were included in analyses.

Design:
This was a randomized controlled wait-list study. Participants were randomized into starting the CBT-I intervention immediately after the baseline assessment or into the wait-list group for 6 weeks before starting CBT-I. Assessments were performed at baseline, 6, 12, and 18 weeks.

Main Measures:
The primary outcome was the Insomnia Severity Index. Secondary measures included the Pittsburg Sleep Quality Index, Post-Concussion Symptom Scale, and Beck Depression and Anxiety Inventories. Statistical analyses included a repeated-measures analysis of variance, t tests, and mixed linear regression modeling.

Results:
There was a group-by-time interaction for the sleep outcomes but not for the concussion or mood outcomes. Differences were seen between groups on sleep outcomes, symptom severity, and depression. The treatment effect was maintained following CBT-I for all outcomes. Improvement in sleep outcomes was predictive of improvement in postconcussion symptom severity and number of symptoms.

Conclusions:
CBT-I reduces insomnia in individuals with concussions, and improved sleep was associated with lower postconcussion and mood symptoms. These effects were maintained 6 to 12 weeks following the intervention.
Systemic medications for sickle cell disease and potential applications for sickle cell retinopathy
Authors: Garg Anupam K. , Scott Adrienne W. 
Published: March 2024

Purpose of review
To review the literature evaluating systemic medications for treatment of sickle cell disease (SCD) and their applications for sickle cell retinopathy.

Recent Findings
Prior studies have demonstrated the efficacy of traditional systemic therapies in reducing the risk of development of sickle cell retinopathy. Since 2017, several new and promising disease-modifying therapies for sickle cell disease have been approved for clinical use, including the first genetic therapies such as exagamglogene autotemcel (exa-cel) and lovotibeglogene autotemcel (lovo-cel). These treatments have shown promising results for systemic management but are not widely utilized due to limited access and high cost. The efficacy of these therapies for the prevention of sickle cell retinopathy remains unknown and opens the door to new avenues for research. Furthermore, the role of systemic therapy for the management of hemoglobin SC (HbSC) disease, which has milder systemic effects but higher likelihood of causing retinopathy, remains poorly understood.

Summary
Hydroxyurea has been a mainstay of systemic management of SCD with prior work suggesting its ability to reduce the likelihood of developing retinopathy. There are several new and potentially curative systemic therapies for SCD, though their role in retinopathy prevention and management has not been studied extensively. Future studies are necessary to understand the implications of these emerging therapies for sickle cell retinopathy.
Peripheral defocus of monofocal intraocular lenses
Authors: Natarajan Ramya , Maceo Heilman Bianca , Ho Arthur , Singh Vivek M. , Ruggeri Marco , Mohamed Ashik , Reddy Jagadesh C. , Parel Jean-Marie A. , Vadavalli Pravin K. , Manns Fabrice 
Published: March 2024

Purpose:
To quantify the angular dependence of monofocal intraocular lens (IOL) power.

Setting:
Ophthalmic Biophysics Laboratory, Kallam Anji Reddy campus, L V Prasad Eye Institute, Hyderabad, India.

Design:
Laboratory study.

Methods:
Experiments were performed on IOLs from 2 different manufacturers (APPALENS 207, Appasamy Associates and SN60WF, Alcon Laboratories, Inc.). IOL powers ranged from 17 to 25 diopters (D). The IOLs were mounted in a fluid-filled chamber, and the on-axis and off-axis powers were measured using a laser ray tracing system over the central 3 mm zone with delivery angles ranging from −30 to +30 degrees in 5-degree increments. The position of the best focus was calculated for each IOL at each angle. The angular dependence of IOL power was compared with theoretical predictions.

Results:
Peripheral defocus increased significantly with increasing incidence angle and power. The peripheral defocus at ±30 degrees increased from 5.8 to 8.5 D when the power increased from 17.5 to 24.5 D for APPALENS 207 and from 4.9 to 7.4 D when the power increased from 17 to 25 D for SN60WF. The mean difference between the measured and theoretical tangential power at ±30 degrees was 0.50 ± 0.16 D for the APPALENS 207 and −0.40 ± 0.10 D for the SN60WF, independent of IOL power.

Conclusions:
IOLs introduce a significant amount of peripheral defocus which varies significantly with IOL power and design. Given that peripheral defocus is related to lens power, replacement of the crystalline lens (approximately 24 D) with an IOL will produce a significant difference in peripheral defocus profile after surgery.
Randomized clinical trial comparing customized corneal crosslinking: epi-on in high oxygen and epi-off in room air for keratoconus
Authors: Elving Sofie , Fredriksson Anneli , Beckman Rehnman Jeannette , Behndig Anders 
Published: March 2024

Purpose:
To compare clinical outcomes of customized transepithelial (epi-on) corneal crosslinking (CXL) in high oxygen and customized CXL with epithelial removal (epi-off) in room air for keratoconus (KC).

Setting:
Umeå University Hospital, Umeå, Sweden.

Design:
Prospective, randomized, single-masked, intraindividually comparing study.

Methods:
32 participants with bilateral progressive KC were treated with bilateral customized topography-guided CXL, 30 mW/cm2; 7.2 to 15 J/cm2 and were randomized to epi-on in one eye (32 eyes) and epi-off in the fellow eye (32 eyes). Uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA), maximal keratometry (Kmax), subjective ocular discomfort, low-contrast visual acuities (LCVAs) at 10% and 2.5% contrast, ocular and anterior corneal wavefront aberrations, manifest refractive spherical equivalent, endothelial cell count (ECC), and adverse events were assessed through 24 months.

Results:
Both treatments showed improvements at 24 months in UDVA; −0.16 ± 0.24 (P < .001) and −0.13 ± 0.20 logMAR (P = .006), respectively, CDVA; −0.10 ± 0.11 (P < .001) and −0.10 ± 0.12 (P = .001), Kmax; −1.74 ± 1.31 (P < .001) and −1.72 ± 1.36 D (P < .001). LCVA 10% improved for both protocols (P < .001), but LCVA 2.5% improved for epi-on CXL only (P = .001). ECC was unaltered, and no adverse events occurred. The epi-on eyes had significantly less discomfort symptoms during the whole first week posttreatment (P < .05).

Conclusions:
High-oxygen customized epi-on CXL is a viable alternative to room air customized epi-off CXL, with faster improvements in CDVA and LCVA and less early ocular discomfort.
Patient Engagement Functionalities’ Influence on Quality Outcomes: The Road via EHR Presence
Authors: Upadhyay Soumya , Bhandari Neeraj 
Published: March 2024

SUMMARY

Goal:
Patients engaged in self-care through information technology can potentially improve the quality of healthcare they receive. This study aimed to examine how electronic health record (EHR) system functionalities help hospitals mediate the impact of patient engagement on quality outcomes—notably, readmission rates.

Methods:
A pooled cross-sectional study design employed data containing 3,547 observations from general acute care hospitals (2014–2018). The breadth of patient engagement functionalities adopted by a hospital was used as the independent variable and the degree of EHR presence was used as the mediating variable. Mean time to readmission for acute myocardial infarction (AMI), pneumonia, and heart failure were the dependent variables. The Baron and Kenny method was used to test mediation.

Principal Findings:
Patient engagement was associated with reduced AMI readmission rates both directly and via EHR system presence. Mediation effects were present, in that a 1-unit increase in patient engagement through EHR system presence was associated with a 0.33% decrease in AMI readmission rates (p < .05). For other disease categories (heart failure and pneumonia), a significant effect was not found.

Practical Applications:
For hospitals with a comprehensive EHR system, patient engagement through information technology can potentially reduce readmission rates for some diseases. More research is needed to determine which specific clinical conditions are amenable to quality improvement through patient engagement. Synergies between patient engagement functionalities and an EHR system positively affect quality outcomes. Therefore, practitioners and hospital managers should leverage hospital investments made in their EHR system infrastructure and use it to engage patients in self-care.