bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene therapy rescues olfactory perception in a clinically relevant ciliopathy model of Bardet–Biedl syndrome
Authors: Xie Chao , Habif Julien C. , Uytingco Cedric R. , Ukhanov Kirill , Zhang Lian , de Celis Carlos , Sheffield Val C. , Martens Jeffrey R. 
Published: August 2021

AbstractBardet–Biedl syndrome (BBS) is a hereditary genetic disorder that results in numerous clinical manifestations including olfactory dysfunction. Of at least 21 BBS‐related genes that can carry multiple mutations, a pathogenic mutation, BBS1M390R, is the single most common mutation of clinically diagnosed BBS outcomes. While the deletion of BBS‐related genes in mice can cause variable penetrance in different organ systems, the impact of the Bbs1M390R mutation in the olfactory system remains unclear. Using a clinically relevant knock‐in mouse model homozygous for Bbs1M390R, we investigated the impact of the mutation on the olfactory system and tested the potential of viral‐mediated, wildtype gene replacement therapy to rescue smell loss. The cilia of olfactory sensory neurons (OSNs) in Bbs1M390R/M390R mice were significantly shorter and fewer than those of wild‐type mice. Also, both peripheral cellular odor detection and synaptic‐dependent activity in the olfactory bulb were significantly decreased in the mutant mice. Furthermore, to gain insight into the degree to which perceptual features are impaired in the mutant mice, we used whole‐body plethysmography to quantitatively measure odor‐evoked sniffing. The Bbs1M390R/M390R mice showed significantly higher odor detection thresholds (reduced odor sensitivity) compared to wild‐type mice; however, their odor discrimination acuity was still well maintained. Importantly, adenoviral expression of Bbs1 in OSNs restored cilia length and re‐established both peripheral odorant detection and odor perception. Together, our findings further expand our understanding for the development of gene therapeutic treatment for congenital ciliopathies in the olfactory system.
Proteomic analysis of ubiquitination substrates reveals a CTLH E3 ligase complex‐dependent regulation of glycolysis
Authors: Maitland Matthew E. R. , Kuljanin Miljan , Wang Xu , Lajoie Gilles A. , Schild‐Poulter Caroline 
Published: August 2021

AbstractUbiquitination is an essential post‐translational modification that regulates protein stability or function. Its substrate specificity is dictated by various E3 ligases. The human C‐terminal to LisH (CTLH) complex is a newly discovered multi‐subunit really interesting new gene (RING) E3 ligase with only a few known ubiquitination targets. Here, we used mass spectrometry‐based proteomic techniques to gain insight into CTLH complex function and ubiquitination substrates in HeLa cells. First, global proteomics determined proteins that were significantly increased, and thus may be substrates targeted for degradation, in cells depleted of CTLH complex member RanBPM. RanBPM‐dependent ubiquitination determined using diGLY‐enriched proteomics and the endogenous RanBPM interactome further revealed candidate ubiquitination targets. Three glycolysis enzymes alpha‐enolase, L‐lactate dehydrogenase A chain (LDHA), and pyruvate kinase M1/2 (PKM) had decreased ubiquitin sites in shRanBPM cells and were found associated with RanBPM in the interactome. Reduced polyubiquitination was validated for PKM2 and LDHA in cells depleted of RanBPM and CTLH complex RING domain subunit RMND5A. PKM2 and LDHA protein levels were unchanged, yet their activity was increased in extracts of cells with downregulated RanBPM. Finally, RanBPM deficient cells displayed enhanced glycolysis and deregulated central carbon metabolism. Overall, this study identifies potential CTLH complex ubiquitination substrates and uncovers that the CTLH complex inhibits glycolysis via non‐degradative ubiquitination of PKM2 and LDHA.
Actions of the NLRP3 and NLRC4 inflammasomes overlap in bone resorption
Authors: Alippe Yael , Kress Dustin , Ricci Biancamaria , Sun Kai , Yang Tong , Wang Chun , Xiao Jianqiu , Abu‐Amer Yousef , Mbalaviele Gabriel 
Published: August 2021

AbstractOverwhelming evidence indicates that excessive stimulation of innate immune receptors of the NOD‐like receptor (NLR) family causes significant damage to multiple tissues, yet the role of these proteins in bone metabolism is not well known. Here, we studied the interaction between the NLRP3 and NLRC4 inflammasomes in bone homeostasis and disease. We found that loss of NLRP3 or NLRC4 inflammasome attenuated osteoclast differentiation in vitro. At the tissue level, lack of NLRP3, or NLRC4 to a lesser extent, resulted in higher baseline bone mass compared to wild‐type (WT) mice, and conferred protection against LPS‐induced inflammatory osteolysis. Bone mass accrual in mutant mice correlated with lower serum IL‐1β levels in vivo. Unexpectedly, the phenotype of Nlrp3‐deficient mice was reversed upon loss of NLRC4 as bone mass was comparable between WT mice and Nlrp3;Nlrc4 knockout mice. Thus, although bone homeostasis is perturbed to various degrees by the lack of NLRP3 or NLRC4, this tissue appears to function normally upon compound loss of the inflammasomes assembled by these receptors.
Responding to Recommended Changes to the 2020–2021 Residency Recruitment Process From a Diversity, Equity, and Inclusion Perspective
Authors: Wilson L. Tamara , Milliken Lindsay , Cagande Consuelo , Stewart Colin 
Published: August 2021

In May 2020, the Coalition for Physician Accountability’s Work Group on Medical Students in the Class of 2021 Moving Across Institutions for Post Graduate Training (WG) released its final report and recommendations. These recommendations pertain to away rotations, virtual interviews, Electronic Residency Application Service opening for programs and the overall residency timeline, and general communications and attempt to provide clarity and level the playing field during the 2020–2021 residency application cycle. The WG’s aims include promoting professional accountability by improving the quality, efficiency, and continuity of the education, training, and assessment of physicians. The authors argue the first 3 WG recommendations may disproportionately impact candidates from historically excluded and underrepresented groups in medicine (HEURGMs) and may affect an institution’s ability to ensure equity in the selection of residency applicants and, thus, warrant further consideration.
The authors examine these recommendations from a diversity, equity, and inclusion (DEI) perspective. For each of the first 3 WG recommendations, the authors highlight new opportunities created by the recommendations and detail challenges that programs must carefully navigate to ensure equity for all candidates. The authors also recommend solutions to guide programs as they address these challenges, meet new common program requirements, and attempt to promote equity for HEURGMs. Finally, the authors recommend that after the 2020–2021 recruitment cycle, the medical education community evaluate DEI-related outcomes of both the WG’s and the authors’ recommendations and incorporate the findings into future application cycles.
Trends in Substance Use Disorder-related Admissions at a Safety-net Hospital, 2008 – 2020
Authors: Lindsay Amber R. , Shearer Riley D. , Bart Gavin , Winkelman Tyler N.A. 
Published: August 2021

Objectives
Safety-net hospitals disproportionately care for people with substance use disorders (SUDs), yet little is known about trends in hospital admissions related to specific substances. This study uses electronic health record data to describe trends in substance-specific admissions at a Midwest urban safety-net hospital.

Methods
We included all admissions from 2008 through 2020 and defined them as non-SUD (N = 154,477) or SUD-related (N = 63,667). We described patient characteristics and trends in substance-specific admissions. We estimated the association of SUD diagnoses with discharge against medical advice and length of stay using logistic regression and generalized linear models.

Results
Between 2008 and 2020, SUD-related admissions increased from 23.1% to 32.9% of total admissions. Admissions related to SUD had significantly more comorbidities than non-SUD-related admissions (4.7 vs 3.5, P < 0.001). Among illicit substances, cocaine-related admissions were the most common in 2008 (3.9% of total admissions, 17.2% of SUD admissions) whereas psychostimulants (eg, methamphetamines) were the most common in 2020 (7.8% of total admissions, 23.8% of SUD admissions). SUD-related hospitalizations had higher rates of against medical advice discharge (3.8%; 95% CI 3.6–3.9 vs 1.4%; 95% CI 1.3–1.4) and longer length of stay (6.3 days; 95% CI: 6.2–6.3 vs 5.3 days; 95% CI: 5.3–5.4) than non-SUD-related admissions.

Conclusions
Over the study period, the proportion of admissions related to substance use rose to approximately one third of all admissions, driven by a rapidly increasing share of psychostimulant-related admissions. Identifying substance use patterns quickly using electronic health record data can help safety-net hospitals meet the needs of their patients and improve outcomes.
Role of Bone Biopsy During Kyphoplasty in the Setting of Known Cancer
Authors: Tariq Muhammad B. , Obedian Richard 
Published: August 2021

Study Design.
Case report.

Objective.
The aim of this study was to emphasize the utility of routine biopsy during kyphoplasty and to report on a unique case of a patient with known history of prostate cancer found to have a new metastatic cancer.

Summary of Background Data.
Vertebral compression fractures (VCFs) may cause debilitating pain with nearly one-third of them leading to chronic pain resulting in a tremendous impact on quality of life in patients. Kyphoplasty has been established as an effective means of surgical treatment. However, routine biopsy during kyphoplasty is presently not the standard of care under the presumption that most VCFs are caused by osteoporosis. The role of biopsy in the setting of known malignancy with multiple other risk factors for VCFs is not well understood.

Methods.
We report on a case of a 73-year-old male with known prostate cancer presenting with persistent unremitting low back pain failing conservative management. Patient develops multiple VCFs in the course of 6 months and is treated with multiple kyphoplasties. Routine biopsy at each level is negative until the last kyphoplasty results positive for malignancy. Surprisingly, the pathology is positive for malignancy other than the patient's known prostate cancer.

Results.
Pathology results prompt oncology workup on the patient which reveals multiple metastases and a new diagnosis of adenocarcinoma of possible upper gastrointestinal origin. In addition, patient's known prostate cancer is also noted to be active. Patient is subsequently started on chemotherapy.

Conclusion.
We highlight the utility of routine biopsy during kyphoplasty especially in patients with known history of malignancy. We emphasize that presumptions about the etiology of a VCF are difficult to make with multiple risk factors and that routine biopsy prevents incorrect presumptions such as in this case.

Level of Evidence: 5
An Experimental Rat Model of C5 Palsy Following Posterior Decompression Surgery of the Cervical Spine
Authors: Yokota Atsushi , Fujishiro Takashi , Usami Yoshitada , Neo Masashi 
Published: August 2021

Study Design.
Basic in vivo research.

Objectives.
The aim of this study was to establish an animal model that is appropriate for analyzing the mechanisms of C5 palsy (C5P) and to clarify the structural and functional alterations of cervical roots following posterior decompression.

Summary of Background Data.
Although C5P is one of the major complications of cervical surgery, the exact pathogenesis of C5P remains unclear partly because of the lack of an appropriate animal model. Tethering of the cervical roots due to posterior cord shift following posterior decompression is thought to be one of the possible factors that cause C5P.

Methods.
Twenty-eight Sprague-Dawley rats were divided into Group L (cervical laminectomy, N = 18) or Group S (sham surgery, N = 10) and examined up to postoperative day 14 (PO14). Posterior cord shift and the length of the anterior rootlets were quantified by computed tomography-myelogram images. Motor evoked potential (MEP) of the deltoid (C5, 6 innervated) and triceps brachii (C7-T1 innervated), mechanical allodynia, and grip strength of the forepaw (C7-T1 regulated) were measured.

Results.
All anterior rootlets were elongated as the cord gradually shifted posteriorly postoperatively. The elongation rate of the C6 anterior rootlets was the highest (142% at PO14). The MEP latency of the deltoid was significantly delayed throughout all postoperative time points. However, significant delay in the latency of the triceps brachii was observed only on postoperative day 10. The withdrawal threshold of the forepaw did not change; grip strength of the forelimb decreased at PO14.

Conclusion.
This model was thought to be appropriate for analyzing the pathogenesis of C5P since our findings were comparable to the clinical course of C5P subsequent to posterior cervical decompression. Although a future study for clarifying histological and molecular alterations will be needed, tethering of the anterior rootlets due to posterior cord shift was suggested to be a probable mechanism causing C5P.

Level of Evidence: 5
RARE PRESENTATION OF BILATERAL CAROTID-CAVERNOUS FISTULA AS SUPRACHOROIDAL HEMORRHAGE DURING CATARACT SURGERY
Authors: Zainol Nurhafis , Raman Puspha , Devi-S Premala , Mohd Khalid Khairul Husnaini 
Published: August 2021

Objective:
To report a rare case of suprachoroidal hemorrhage during phacoemulsification in a patient with bilateral carotid-cavernous fistula.

Method:
Case report.

Result:
A 76-year-old woman with underlying hypertension presented left eye poor vision due to an underlying dense cataract. Her initial preoperative assessment was uneventful, and she underwent phacoemulsification. During epinucleus removal, there was sudden, unexpected anterior chamber shallowing, resulting in posterior capsule rupture. While the surgeon extended the wound to facilitate epinucleus removal, there was a further decrease of red reflex, followed by hardening of the globe, indicating a suprachoroidal hemorrhage. The corneal wound was opposed swiftly without an intraocular lens. Further evaluation after that revealed the patient had a chronic headache for several years, and ocular examination showed bilateral esophoria. A computed tomography demonstrated features suggestive of bilateral carotid-cavernous fistula, which was confirmed with computed tomography angiography later.

Conclusion:
Patients with carotid-cavernous fistula have elevated episcleral venous pressure and vortex venous pressure. Sudden decompression of the globe in these patients predisposes them to higher suprachoroidal hemorrhage risk, although this condition is generally rare in phacoemulsification.
Pneumonia, Sinusitis, Influenza and Other Respiratory Illnesses in Acute Otitis Media–Prone Children
Authors: Pichichero Michael E. , Chapman Timothy J. , Bajorski Peter 
Published: August 2021

Background:
Recurrent acute otitis media in the first years of life can be explained by immune dysfunction. Consequently, it would be expected that otitis-prone (OP) children would be more susceptible to other infectious diseases, especially respiratory infections, since a component of the immune problem involves nasopharyngeal innate immunity.

Design:
Cohort study with prospective identification of all physician-diagnosed, medically attended respiratory illness visits in children 6 months to 5 years of age to determine the incidence of pneumonia, acute sinusitis, influenza and other bacterial and viral infections among OP compared with non-OP (NOP) children. Tympanocentesis to microbiologically confirm acute otitis media disease.

Results:
Two hundred eighty-five children were studied. Thirty-nine met a standard definition of stringently defined OP (sOP) determined by tympanocentesis and 246 were NOP. sOP children had increased frequency of presumptive respiratory infections, pneumonia (6-fold higher, P < 0.001), sinusitis (2.1-fold higher, P = 0.026) and influenza (2.9-fold higher, P = 0.002), compared with NOP children. Demographic and risk factor covariate-adjusted fold difference between sOP and NOP children for all respiratory infection illness visits was 2.4-fold (P < 0.00001) at 6–18 months of age, 2.2-fold (P < 0.00001) at 18–30 months of age and at age and 2.4-fold (P = 0.035) higher at 30 to 42 months. For both sOP and NOP children, more frequent medically attended respiratory infection illness visits from 6–18 months of age predicted more frequent visits experienced from 18–60 months of age.

Conclusions:
Clinicians should be aware of a significant increased likelihood of bacterial and viral respiratory infection proneness among OP children.
Effect of Timing of Intravenous Ketorolac Administration on Pain in Orbitotomy Surgery
Authors: Lee Kathryn W. , Tram Justin , Wladis Edward J. 
Published: August 2021

Purpose:
Intravenous ketorolac (IVK) is an effective and safe medication to reduce postoperative pain in the setting of oculofacial surgery. This study was undertaken to determine the impact of timing of IVK administration in orbital surgery on the reduction of postoperative pain score and opioid requirement.

Methods:
Patients either received IVK immediately before (n = 50), during (n = 50) or after (n = 50) orbital surgery or acted as controls (n = 50). Pain scores were assessed via an analog scale immediately after surgery and on the first postoperative day. The requirements for opioid analgesics were recorded. Statistical analyses were performed via a dedicated computerized software package.

Results:
One hundred fifty patients received IVK; 50 before incision (28 males, 22 females, mean age 52.2), 50 intraoperatively (20 males, 30 females, mean age 49.8) and 50 in the immediate postoperative period (26 males, 24 females, mean age = 55.3). Additionally, 50 patients acted as controls (26 males, 24 females, mean age 54). Immediately after surgery, administration of IVK resulted in statistically significant reduction in pain score regardless of the timing of dosing as compared with control patients (prior = 2.36, intraoperative = 2.34, postoperative = 2.46 vs. control 5.44, p < 0.0001). Eleven patients (22%) in the control group required opioids, whereas, in the IVK cohorts, only 2 (4%—preoperative), 1 (2%—intraoperative), and 1 (2%—postoperative) patients needed these medications (p = 0.0039).

Conclusions:
In the setting of orbital surgery, IVK reduced pain scores and opioid requirement, regardless of the timing of administration, as compared with patients that did not receive the medication.
Health Literacy Levels of Women and Related Factors in Turkey
Authors: AYAZ-ALKAYA Sultan , OZTURK Fatma Ozlem 
Published: August 2021

ABSTRACT

Background
Health literacy is a complex issue affecting the health outcomes of women and their families.

Purpose
This study was conducted to determine the health literacy levels and related factors of women attending various courses in family centers of a municipality.

Methods
This cross-sectional research was conducted on a sample of women enrolled in various courses at eight family centers in a city center. The sample consisted of 837 women who agreed to participate. The participation rate was 76%. Two different health literacy scales were used to collect data for analysis.

Results
Of the women, 50.4% were over 40 years old, 35.2% were high school graduates, 89.6% were not working, 53.2% self-reported their monthly income as equal to their monthly expenses, 88.8% had social security, 28.4% had chronic diseases, 29.2% used medication regularly, 35.2% had visual problems, 7.8% had hearing problems, and 77.9% used the internet. According to the results of the Turkish Health Literacy Scale, 45.9% of the participants were in the inadequate category, 30.6% were in the inadequate and limited category, 16.0% were in the adequate category, and 7.4% were in the excellent category. Women aged 40 years and over, those who were elementary school graduates, those who had visual and hearing problems, those who used eyewear, those whose monthly income was less than expenses, and those who were non-internet users respectively had mean health literary scores that were significantly below the mean score for all participants (p < .05).

Conclusions/Implications for Practice
The largest number of participants was categorized has having a “low-insufficient” level of health literacy. Age, educational level, income, having visual and hearing problems, wearing glasses, and internet use were found to affect level of health literacy. For this reason, factors such as age, educational level, income, vision and hearing problems, use of eyeglasses, and internet use should be considered when planning initiatives to increase health literacy in women.
Effect of Solution-Focused Therapy on Cancer-Related Fatigue in Patients With Colorectal Cancer Undergoing Chemotherapy
Authors: Xian Xuemei , Zhu Chenping , Chen Yilin , Huang Binbin , Xiang Weilan 
Published: August 2021

Background
Cancer-related fatigue (CRF) has gained increased attention in the past decade but remains difficult to treat. It is a predictor of patients’ overall health and quality of life (QoL). Therefore, controlling fatigue is important for patients with cancer.

Objective
The aim of this study was to test the effect of solution-focused therapy (SFT) in reducing CRF and improving QoL in patients with colorectal cancer (CRC) undergoing chemotherapy.

Methods
A total of 124 patients with CRC undergoing chemotherapy were recruited and randomized to the SFT group or control group. Cancer-related fatigue was measured with the Cancer Fatigue Scale–Chinese version (CFS-C) at baseline, 3 months, and 6 months. Quality of life was measured with the Quality of Life Instruments for Colorectal Cancer Patients at baseline and 6 months.

Results
Of 124 patients, 119 (95.9%) were evaluable. The SFT group showed significantly lower Cancer Fatigue Scale–Chinese version scores than the control group in all subscales and the total scores at 3 months (P < .001). At 6 months, the SFT group had significantly lower scores in cognitive fatigue (P < .001) and total fatigue (P = .005). The CRF of the SFT group decreased in the first 3 months (P = .012) but increased at 6 months (P < .001). The SFT group had significantly higher scores in the physical and psychological domains and overall QoL (P = .002, P <.001, and P = .02) than the control group at 6 months.

Conclusion
Solution-focused therapy may decrease the CRF and improve QoL during chemotherapy for patients with CRC.

Implication for Practice
Solution-focused therapy can be implemented to relieve fatigue and improve QoL in patients with CRC.