bluuebunny/crossref_metadata_2025_split huggingface dataset:
NOVEL APPLICATION OF DEEP ANTERIOR LAMELLAR KERATOPLASTY FOR RETINAL DETACHMENT REPAIR IN TOTALLY OPAQUE CORNEA SECONDARY TO ANIRIDIA
Authors: Simpson Alasdair Innes , Al-Hayouti Huda , Ramaesh Kanna , Saidkasimova Shohista 
Published: August 2023

Purpose:
We present a novel approach for managing retinal detachment in a patient with aniridia-related corneal scarring precluding fundal view through a deep anterior lamellar keratoplasty.

Methods:
A 30-year-old female patient who had bilaterally opaque cornea, due to advanced aniridia-related keratopathy presented with, experiencing flashing of light in her right eye. Examination of the retinal fundus was not possible because of the dense corneal scarring and underlying cataract. A superior bullous macula-off retinal detachment was diagnosed on ultrasonography. VA at presentation was hand motions. The corneal scarring extended to the mid-to-deep stroma. We performed a deep anterior lamellar dissection of the opacified corneal stroma, which allowed clear visualization of a dense cataract. The cataract was removed by phacoemulsification and intraocular lens (IOL) inserted. This allowed to proceeding with repair of retinal detachment through pars plana approach. The surgery was completed by a donor deep lamellar keratoplasty.

Results:
This achieved a good fundal view to proceed with phacovitrectomy visualized through the residual corneal layers. Uneventful pars plana vitrectomy, cryotherapy, and sulfur hexafluoride (SF6) gas were performed to reattach the retina. Postoperatively, the graft remains clear at 6 months with a VA of 20/160 in the right eye, a level of vision the patient had not experienced for decades.

Conclusion:
Deep anterior lamellar keratoplasty offered an alternative to temporary keratoprosthesis to achieve a clear view of the retinal fundus and perform pars plana vitrectomy and repair of the retinal detachment.
Predicting direct healthcare costs of general practitioner–guided care in patients with musculoskeletal complaints
Authors: Pellekooren Sylvia , Ben Ângela J. , van Dongen Johanna M. , Pool-Goudzwaard Annelies L. , van Tulder Maurits W. , van den Berg Jesse M. , Ostelo Raymond W.J.G. 
Published: August 2023

Abstract
Information on healthcare utilization and costs of general practitioner (GP)–guided care in patients with musculoskeletal complaints is important for keeping healthcare affordable and accessible. A registry-based study was performed to describe healthcare utilization and costs of GP-guided care in patients with musculoskeletal complaints and to predict having higher direct healthcare costs. Healthcare costs of GP-guided care included all healthcare resources used by patients due to a musculoskeletal condition in 2018. Data were extracted from the database with a 1-year follow-up and descriptively analyzed. A general linear model was developed to predict having higher direct healthcare costs. In total, 403,719 patients were included, of whom 92% only received a single consultation. The number of referrals varied across the different types of complaints. Total annual direct healthcare costs amounted to €39,180,531, of which a key cost driver was referrals. Primary care consultations accounted for the largest part of referral-related costs. For all musculoskeletal conditions combined, the mean annual direct healthcare cost per patient was €97 (SEM = €0.18). Older age, being a woman, low socioeconomic status, spine complaints, high number of musculoskeletal diagnoses, and a high comorbidity score were predictive of having higher direct healthcare costs and explained 0.7% of the variance. This study showed that mean annual direct healthcare costs of GP-guided care in patients with musculoskeletal conditions were relatively low and did not differ considerably across conditions. The predictive model explained a negligible part of the variance in costs. Thus, it is unclear which factors do predict high direct healthcare costs in this population.
The Validity and Reliability of the Workplace Culture of Health Scale–Short Form
Authors: Marenus Michele W. , Marzec Mary , Kilbourne Amy , Colabianchi Natalie , Chen Weiyun 
Published: August 2023

Objective
A positive workplace culture of health can have significant benefits for both employees and organizations. The objective of this study was to test the validity and reliability of the Workplace Culture of Health (COH) Scale–Short Form.

Methods
We conducted a confirmatory factor analysis on data collected from a sample of 12,907 employees across 14 organizations. We examined the construct validity of the 14-item short-form version of the Workplace COH scale and assessed its reliability using internal consistency measures.

Results
Our confirmatory factor analysis demonstrated that the Workplace COH Scale–Short Form had strong model fit, indicating good construct validity. In addition, we found that all constructs had strong internal consistency reliability.

Conclusions
Findings suggest that the Workplace COH Scale–Short Form is a valid and reliable way to practically assess workplace culture of health from the employee perspective.
Long-term outcomes (beyond 5 years) of liver transplant recipients—A transatlantic multicenter study
Authors: Palaniyappan Naaventhan , Peach Emily , Pearce Fiona , Dhaliwal Amritpal , Campos-Varela Isabel , Cant Matthew R. , Dopazo Cristina , Trotter James , Divani-Patel Sapna , Hatta Ayiesha A.Z. , Hopkins Laurence , Testa Giuliano , Bilbao Angela , Kasmani Zain , Faloon Sarah , Mirza Darius F. , Klintmalm Goran B. , Bilbao Itxarone , Asrani Sumeet K. , Rajoriya Neil , Aravinthan Aloysious D. 
Published: August 2023

The long-term (>5 y) outcomes following liver transplantation (LT) have not been extensively reported. The aim was to evaluate outcomes of LT recipients who have survived the first 5 years. A multicenter retrospective analysis of prospectively collected data from 3 high volume LT centers (Dallas-USA, Birmingham-UK, and Barcelona-Spain) was undertaken. All adult patients, who underwent LT since the inception of the program to December 31, 2010, and survived at least 5 years since their LT were included. Patient survival was the primary outcome. A total of 3682 patients who survived at least 5 years following LT (long-term survivors) were included. Overall, median age at LT was 52 years (IQR 44–58); 53.1% were males; and 84.6% were Caucasians. A total of 49.4% (n=1820) died during a follow-up period of 36,828 person-years (mean follow-up 10 y). A total of 80.2% (n=1460) of all deaths were premature deaths. Age-standardized all-cause mortality as compared to general population was 3 times higher for males and 5 times higher for females. On adjusted analysis, besides older recipients and older donors, predictors of long-term mortality were malignancy, cardiovascular disease, and dialysis. Implementation of strategies such as noninvasive cancer screening, minimizing immunosuppression, and intensive primary/secondary cardiovascular prevention could further improve survival.
CTNNB1 and APC Mutations in Sinonasal Myxoma
Authors: Chen Sonja , Gallant Sara , Cunningham Michael J. , Robson Caroline D. , Church Alanna J. , Perez-Atayde Antonio R. , Al-Ibraheemi Alyaa 
Published: August 2023

Sinonasal myxoma (SNM) is a rare, benign mesenchymal neoplasm with distinct clinicopathologic features and aberrant nuclear localization of β-catenin by immunohistochemistry. The molecular underpinnings have been linked to that of a “myxoid variant” of desmoid fibromatosis. Herein, we describe a series of 8 cases of SNM and propose clinical and biologic differences compared with desmoid fibromatosis. Our patient cohort is comprised of 5 males and 3 females (age range: 10 mo to 12 y), 6 of whom are aged less than or equal to 24 months. All presented with facial swelling, reflecting lesions involving the maxillary bone, and all underwent resection. All tumors were variably cellular and comprised of bland spindled to stellate cells in a profusely myxoid background with diffuse nuclear β-catenin expression. All cases of SNM were analyzed by next-generation sequencing using the Oncopanel assay. Three cases failed sequencing, 2 of 5 successful cases exhibited exon 3 CTNNB1 alterations involving the ubiquitin recognition motif, and 3 had adenomatous polyposis coli (APC) deletions. One patient had APC germline testing which was negative. No germline testing was available for the remaining 7 patients. Follow-up data over a range of 1 month to 23 years was available for 7 of the 8 SNMs. One case patient had local recurrence, and all were alive without evidence of disease. This is in contrast to the high recurrence rate typically seen in desmoid fibromatosis, particularly after resection. Our findings expand the spectrum of tumors with underlying WNT/β-catenin pathway and highlight the histologic, clinical, and genetic differences of SNM compared with desmoid fibromatosis. APC deletion raises the possibility of underlying germline alteration and familial adenomatous polyposis.
Different coexistence patterns between apex carnivores and mesocarnivores based on temporal, spatial, and dietary niche partitioning analysis in Qilian Mountain National Park, China
Authors: Cong Wei , Li Jia , Hacker Charlotte , Li Ye , Zhang Yu , Jin Lixiao , Zhang Yi , Li Diqiang , Xue Yadong , Zhang Yuguang 
Published: August 2023

AbstractCarnivores play key roles in maintaining ecosystem structure and function as well as ecological processes. Understanding how sympatric species coexist in natural ecosystems is a central research topic in community ecology and biodiversity conservation. In this study, we explored intra- and interspecific niche partitioning along spatial, temporal, and dietary niche partitioning between apex carnivores (wolfCanis lupus, snow leopardPanthera uncia, Eurasian lynxLynx lynx) and mesocarnivores (Pallas’s catOtocolobus manul, red foxVulpes vulpes, Tibetan foxVulpes ferrilata) in Qilian Mountain National Park, China using camera trapping data and DNA metabarcoding sequencing data. Our study showed that apex carnivore species had more overlap temporally (coefficients of interspecific overlap ranging from 0.661 to 0.900) or trophically (Pianka’s index ranging from 0.458 to 0.892), mesocarnivore species had high dietary overlap with each other (Pianka’s index ranging from 0.945 to 0.997), and apex carnivore and mesocarnivore species had high temporal overlap (coefficients of interspecific overlap ranging from 0.497 to 0.855). Large dietary overlap was observed between wolf and snow leopard (Pianka’s index=0.892) and Pallas’s cat and Tibetan fox (Pianka’s index=0.997), suggesting the potential for increased resource competition for these species pairs. We concluded that spatial niche partitioning is likely to key driver in facilitating the coexistence of apex carnivore species, while spatial and temporal niche partitioning likely facilitate the coexistence of mesocarnivore species, and spatial and dietary niche partitioning facilitate the coexistence between apex and mesocarnivore species. Our findings consider partitioning across temporal, spatial and dietary dimensions while examining diverse coexistence patterns of carnivore species in Qilian Mountain National Park, China. These findings will contribute substantially to current understanding of carnivore guilds and effective conservation management in fragile alpine ecosystems.
TLR2 Regulates Hair Follicle Cycle and Regeneration via BMP Signaling
Authors: Xiong Luyang , Zhevlakova Irina , West Xiaoxia Z. , Gao Detao , Murtazina Rakhylia , Horak Anthony , Brown J. Mark , Molokotina Iuliia , Podrez Eugene A. , Byzova Tatiana V. 
Published: August 2023

AbstractThe etiology of hair loss remains enigmatic, and current remedies remain inadequate. Transcriptome analysis of aging hair follicles uncovered changes in immune pathways, including Toll-like receptors (TLRs). Our findings demonstrate that the maintenance of hair follicle homeostasis and the regeneration capacity after damage depends on TLR2 in hair follicle stem cells (HFSCs). In healthy hair follicles, TLR2 is expressed in a cycle-dependent manner and governs HFSCs activation by countering inhibitory BMP signaling. Hair follicles in aging and obesity exhibit a decrease in both TLR2 and its endogenous ligand carboxyethylpyrrole (CEP), a metabolite of polyunsaturated fatty acids. Administration of CEP stimulates hair regeneration through a TLR2-dependent mechanism. These results establish a novel connection between TLR2-mediated innate immunity and HFSC activation, which is pivotal to hair follicle health and the prevention of hair loss and provide new avenues for therapeutic intervention.SummaryHair follicle stem cells TLR2 is required for hair homeostasis and regeneration. While TLR2 stimulation by endogenous ligand promotes hair growth, reduction in TLR2 and its ligand in aging and obesity may diminish hair growth.
IRF5 regulates microglial myelin clearance and cholesterol metabolism after demyelination
Authors: Montilla Alejandro , Zabala Alazne , Calvo Ibai , Mata Paloma , Tomé Irene , Koster Mirjam , Sierra Amanda , Kooistra Susanne M. , Soria Federico Nicolás , Eggen Bart J.L. , Fresnedo Olatz , Fernández José Andrés , Tepavcevic Vanja , Matute Carlos , Domercq María 
Published: August 2023

AbstractInterferon regulatory factor 5 (IRF5), a transcription factor highly involved in innate immunity that drives microglia/macrophage towards a pro-inflammatory state, has been associated to multiple sclerosis susceptibility but its role in MS pathogenesis is unknown. Here we analysed the role of IRF5 in multiple sclerosis animal models.Irf5-/-mice showed exacerbated damage in the chronic phase of experimental autoimmune encephalomyelitis (EAE) mice, despite an initial delay in its onset, as well as after lysolecithin injection into the spinal cord. Transcriptomic and lipidomic analysis evidence a role of this transcription factor in myelin metabolism and cholesterol homeostasis. Indeed,Irf5-/-mice showed an aberrant accumulation of myelin debris and lipidic structures, such as CE-containing lipid droplets and cholesterol crystals, suggesting that myelin-derived lipids are not properly processed. Cholesterol crystal accumulation leads to an aberrant inflammatory response, which block oligodendrocyte migration into the core of demyelinated lesion and remyelination. Pharmacologically facilitating cholesterol transport reduces lipid droplet accumulation and ameliorates EAE exacerbated damage inIrf5-/-mice. These results reveal for the first time the role of Irf5, a transcription factor necessary to orchestrate the immune responses, in phagocytes lipid metabolism which could be pivotal in regenerative responses such as remyelination.
Dietary amino acids and risk of stroke subtypes: a prospective analysis of 356,000 participants in seven European countries
Authors: Tong Tammy Y.N. , Clarke Robert , Schmidt Julie A. , Huybrechts Inge , Noor Urwah , Forouhi Nita G. , Imamura Fumiaki , Travis Ruth C. , Weiderpass Elisabete , Aleksandrova Krasimira , Dahm Christina C. , van der Schouw Yvonne T. , Overvad Kim , Kyrø Cecilie , Tjønneland Anne , Kaaks Rudolf , Katzke Verena , Schiborn Catarina , Schulze Matthias B. , Mayen-Chacon Ana-Lucia , Masala Giovanna , Sieri Sabina , de Magistris Maria Santucci , Tumino Rosario , Sacerdote Carlotta , Boer Jolanda M.A. , Verschuren W.M. Monique , Brustad Magritt , Nøst Therese Haugdahl , Crous-Bou Marta , Petrova Dafina , Amiano Pilar , Huerta José María , Moreno-Iribas Conchi , Engström Gunnar , Melander Olle , Johansson Kristina , Lindvall Kristina , Aglago Elom K. , Heath Alicia K. , Butterworth Adam S. , Danesh John , Key Timothy J. 
Published: August 2023

AbstractBackgroundPreviously reported associations of protein-rich foods with stroke subtypes have prompted interest in assessment of individual amino acids. We examined the associations of dietary amino acids with risks of ischaemic and haemorrhagic stroke in the EPIC study.MethodsWe analysed data on 356,142 participants from seven European countries. Dietary intakes of 19 individual amino acids were assessed using validated country-specific dietary questionnaires, calibrated using additional 24-hour dietary recalls. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of ischaemic and haemorrhagic stroke in relation to intake of each amino acid. The role of blood pressure as a potential mechanism was assessed in 267,642 (75%) participants.ResultsAfter a median follow-up of 12.9 years, 4,295 participants had an ischaemic stroke and 1,375 participants had a haemorrhagic stroke. After correction for multiple testing, higher intake of proline (as percent of total protein) was associated with 12% lower risk of ischaemic stroke (HR per 1 SD higher intake 0.88; 95% CI 0.82, 0.94). The association persisted after mutual adjustment for all other amino acids, systolic and diastolic blood pressure. The inverse associations of isoleucine, leucine, valine, phenylalanine, threonine, tryptophan, glutamic acid, serine and tyrosine with ischaemic stroke were each attenuated with adjustment for proline intake. For haemorrhagic stroke, no statistically significant associations were observed in the continuous analyses after correcting for multiple testing.ConclusionHigher proline intake was associated with a lower risk of ischaemic stroke, independent of other dietary amino acids and blood pressure.
Plasmatic HIV-1 soluble gp120 is associated with immune dysfunction and inflammation in ART-treated individuals with undetectable viremia
Authors: Benlarbi Mehdi , Richard Jonathan , Bourassa Catherine , Tolbert William D. , Chartrand-Lefebvre Carl , Gendron-Lepage Gabrielle , Sylla Mohamed , El-Far Mohamed , Messier-Peet Marc , Guertin Camille , Turcotte Isabelle , Fromentin Rémi , Verly Myriam Maude , Prévost Jérémie , Clark Andrew , Mothes Walther , Kaufmann Daniel E. , Maldarelli Frank , Chomont Nicolas , Bégin Philippe , Tremblay Cécile , Baril Jean-Guy , Trottier Benoit , Trottier Sylvie , Duerr Ralf , Pazgier Marzena , Durand Madeleine , Finzi Andrés ,   the Canadian HIV,   Aging Cohort Study
Published: August 2023

ABSTRACTBackgroundChronic inflammation persists in some people living with HIV (PLWH), even during antiretroviral therapy (ART) and is associated with premature aging. The gp120 subunit of the HIV-1 envelope glycoprotein can shed from viral and cellular membranes and can be detected in plasma and tissues, showing immunomodulatory properties even in the absence of detectable viremia. We evaluated whether plasmatic soluble gp120 (sgp120) and a family of gp120-specific anti-cluster A antibodies, which were previously linked to CD4 depletionin vitro, could contribute to chronic inflammation, immune dysfunction, and sub-clinical cardiovascular disease in participants of the Canadian HIV and Aging cohort (CHACS) with undetectable viremia.MethodsCross-sectional assessment of plasmatic sgp120 and anti-cluster A antibodies was performed in 386 individuals from CHACS. Their association with pro-inflammatory cytokines, as well as subclinical coronary artery disease measured by computed tomography coronary angiography was assessed using linear regression models.ResultsIn individuals with high levels of sgp120, anti-cluster A antibodies inversely correlated with CD4 count (p=0.042) and CD4:CD8 ratio (p=0.004). The presence of sgp120 was associated with increased plasma levels of IL-6. In participants with detectable atherosclerotic plaque and detectable sgp120, sgp120 levels, anti-cluster A antibodies and their combination correlated positively with the total volume of atherosclerotic plaques (p=0.01, 0.018 and 0.006, respectively).ConclusionSoluble gp120 may act as a pan toxin causing immune dysfunction and sustained inflammation in a subset of PLWH, contributing to the development of premature comorbidities. Whether drugs targeting sgp120 could mitigate HIV-associated comorbidities in PLWH with suppressed viremia warrants further studies.Key pointsSoluble gp120 is detected in the plasma of people living with HIV-1 with undetectable viremia. The presence of soluble gp120 and anti-cluster A antibodies is associated with immune dysfunction, chronic inflammation, and sub-clinical cardiovascular disease.
Shedding Light on the Dark Genome: Insights into the Genetic, CRISPR-based, and Pharmacological Dependencies of Human Cancers and Disease Aggressiveness
Authors: Kafita Doris , Nkhoma Panji , Dzobo Kevin , Sinkala Musalula 
Published: August 2023

AbstractInvestigating the human genome is vital for identifying risk factors and devising effective therapies to combat genetic disorders and cancer. Despite the extensive knowledge of the “light genome”, the poorly understood “dark genome” remains understudied. In this study, we integrated data from 20,412 protein-coding genes in Pharos and 8,395 patient-derived tumours from The Cancer Genome Atlas (TCGA) to examine the genetic and pharmacological dependencies in human cancers and their treatment implications. We discovered that dark genes exhibited high mutation rates in certain cancers, similar to light genes. By combining the drug response profiles of cancer cells with cell fitness post-CRISPR-mediated gene knockout, we identified the crucial vulnerabilities associated with both dark and light genes. Our analysis also revealed that tumours harbouring dark gene mutations displayed worse overall and disease-free survival rates than those without such mutations. Furthermore, dark gene expression levels significantly influenced patient survival outcomes. Our findings demonstrated a similar distribution of genetic and pharmacological dependencies across the light and dark genomes, suggesting that targeting the dark genome holds promise for cancer treatment. This study underscores the need for ongoing research on the dark genome to better comprehend the underlying mechanisms of cancer and develop more effective therapies.