bluuebunny/crossref_metadata_2025_split huggingface dataset:
An in vitro investigation into the impact of corneal rinsing on riboflavin/UVA corneal cross-linking
Authors: Morgan Siân R. , O’Brart David P. S. , Huang Jinhai , Meek Keith M. , Hayes Sally 
Published: February 2024

Abstract
Background
Corneal cross-linking (CXL) using riboflavin and ultraviolet-A light (UVA) is a treatment used to prevent progression of keratoconus. This ex vivo study assesses the impact on CXL effectiveness, as measured by tissue enzymatic resistance and confocal microscopy, of including a pre-UVA corneal surface rinse with balanced salt solution (BSS) as part of the epithelium-off treatment protocol.

Methods
Sixty-eight porcine eyes, after epithelial debridement, were assigned to six groups in three experimental runs. Group 1 remained untreated. Groups 2–6 received a 16-min application of 0.1% riboflavin/Hydroxypropyl methylcellulose (HPMC) drops, after which Group 3 was exposed to 9 mW/cm2 UVA for 10 min, and Groups 4–6 underwent corneal surface rinsing with 0.25 mL, 1 mL or 10 mL BSS followed by 9 mW/cm2 UVA exposure for 10 min. Central corneal thickness (CCT) was recorded at each stage. Central 8.0 mm corneal buttons from all eyes were subjected to 0.3% collagenase digestion at 37 °C and the time required for complete digestion determined. A further 15 eyes underwent fluorescence confocal microscopy to assess the impact of rinsing on stromal riboflavin concentration.

Results
Application of riboflavin/HPMC solution led to an increase in CCT of 73 ± 14 µm (P < 0.01) after 16 min. All CXL-treated corneas displayed a 2–4 fold greater resistance to collagenase digestion than non-irradiated corneas. There was no difference in resistance between corneas that received no BSS rinse and those that received a 0.25 mL or 1 mL pre-UVA rinse, but each showed a greater level of resistance than those that received a 10 mL pre-UVA rinse (P < 0.05). Confocal microscopy demonstrated reduced stromal riboflavin fluorescence after rinsing.

Conclusions
All protocols, with and without rinsing, were effective at enhancing the resistance to collagenase digestion, although resistance was significantly decreased, and stromal riboflavin fluorescence reduced with a 10 mL rinse. This suggests that a 10 mL surface rinse can reduce the efficacy of CXL through the dilution of the stromal riboflavin concentration.
Renal function and lipid metabolism in Japanese HIV-1-positive individuals 288 weeks after switching from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate: a single-center, retrospective cohort study
Authors: Abe Kensuke , Imamura Junji , Sasaki Akiko , Suzuki Tomoko , Kamio Satomi , Obara Taku , Ito Toshihiro 
Published: February 2024

Abstract
Background
Continued use of tenofovir disoproxil fumarate (TDF), an antiretroviral drug, causes renal function decline and tubular damage in individuals with HIV. While tenofovir alafenamide fumarate (TAF) may have less damaging effects, it causes weight gain and abnormal lipid metabolism.

Methods
This single-center, retrospective cohort study used medical records from the National Hospital Organization Sendai Medical Center to investigate renal function of Japanese HIV-1-positive individuals who switched from TDF to antiretroviral therapy including TAF by 2017. The endpoints were: estimated glomerular filtration rate (eGFR), urinary β2 microglobulin (Uβ2MG), weight, and lipid metabolism parameters at 288 weeks after switching. Possible correlation between eGFR and Uβ2MG and factors affecting eGFR decline were examined.

Results
Sixty patients switched from TDF to TAF and continued therapy for 288 weeks. eGFR showed a significant decline after 144 weeks, although it was controlled from the time of change until 96 weeks. In the renal impairment group, the decline was suppressed until week 288. Uβ2MG continued to decrease significantly after 48 weeks. However, the suggested correlation between eGFR and Uβ2MG disappeared when patients switched from TDF to TAF. Weight and lipid metabolic parameters increased significantly at 48 weeks and were maintained. Factors associated with decreased eGFR were: history of acquired immune deficiency syndrome (AIDS) and Uβ2MG. However, considering the odds ratio, the switch from TDF to TAF suppressed the eGFR decline in the group with a history of AIDS, and Uβ2MG had no effect on the eGFR decline.

Conclusions
Switching from TDF to TAF for the long term slows eGFR decline, decreases Uβ2MG levels, and reduces worsening of renal function. Weight gain and abnormal lipid metabolism may occur in the short term but are controllable.
Exercise therapy, education, and cognitive behavioral therapy alone, or in combination with total knee arthroplasty, in patients with knee osteoarthritis: a randomized feasibility study
Authors: Rognsvåg Turid , Bergvad Ingvild Buset , Furnes Ove , Indrekvam Kari , Lerdal Anners , Lindberg Maren Falch , Skou Søren T , Stubberud Jan , Badawy Mona 
Published: February 2024

Abstract
Background
One in five patients experience chronic pain 1 year after total knee arthroplasty (TKA), highlighting the need for enhanced treatment strategies to improve outcomes. This feasibility trial aimed to optimize the content and delivery of a complex intervention tailored to osteoarthritis (OA) patients at risk of poor outcome after TKA and assess the feasibility of initiating a full-scale multicenter randomized controlled trial (RCT).

Methods
Patients scheduled for TKA were included between August 2019 and June 2020 and block-randomized into one of three groups: (a) 12-week exercise therapy and education (ExE) and 10-module internet-delivered cognitive behavioral therapy (iCBT), (b) TKA followed by ExE and iCBT and (c) TKA and standard postoperative care. Outcomes were (i) recruitment and retention rate, (ii) compliance to the intervention and follow-up, (iii) crossover, and (iv) adverse events, reported by descriptive statistics.

Results
Fifteen patients were included in the study. Only 1 out of 146 patients screened for eligibility was included during the first 4 months. During the next 3 months, 117 patients were not included since they lived too far from the hospital. To increase the recruitment rate, we made three amendments to the inclusion criteria; (1) at-risk screening of poor TKA outcome was removed as an eligibility criterion, (2) patients across the country could be included in the study and (3) physiotherapists without specific certification were included, receiving thorough information and support. No patients withdrew from the study or crossed over to surgery during the first year. Nine out of 10 patients completed the ExE program and six out of 10 completed the iCBT program. Fourteen out of 15 patients completed the 1-year follow-up. One minor adverse event was registered.

Conclusions
Except for recruitment and compliance to iCBT, feasibility was demonstrated. The initial recruitment process was challenging, and necessary changes were made to increase the recruitment rate. The findings informed how a definitive RCT should be undertaken to test the effectiveness of the complex intervention.

Trial registration
The MultiKnee RCT, including the feasibility study, is pre-registered at ClinicalTrials.gov: NCT03771430 11/12/2018.
Adopting Gartner’s hype cycles to investigate the lifespan of computer assisted language learning from EFL learners' perspectives
Authors: Meihami Hussein , Alexander Christopher 
Published: February 2024

AbstractIt is crucial to study how L2 learners use technology when examining the lifespan technology in L2 pedagogy. Therefore, we adopted Gartner’s hype cycles to investigate the lifespan of CALL from the perspectives of EFL learners. To this end, we utilized an explanatory narrative design and gathered and analysed the perspectives of 87 EFL learners regarding the CALL lifespan using autobiographical narratives and semi-structured interviews. The results of the deductive thematic analysis presented motivating and demotivating factors that were asserted to affect EFL learners’ uptake of CALL technologies. Moreover, the findings revealed that EFL learners had fallacies about CALL in the first stages of using technology for L2 learning and tended to reduce those fallacies later on. Therefore, it can be concluded that EFL learners start their use of CALL with some misconceptions stemming from the motivating factors of CALL, continue their use of CALL by facing some demotivating factors originating from fallacies about CALL that they have already committed, and finalise their use of CALL by exploring about CALL features that help them avoid their fallacies. The study has implications to shorten the time of reaching the awareness zone by the L2 learners.
Impact of Parkinsonism comorbid depression on cognitive functions
Authors: Shehata Ghaydaa A. , Farweez Hassan M. , Ali Anwar M. , Hassan Huda S. , Tohamy Amal M. , Mostafa Mohamed , Ibrahim Mostafa A. , Tarek Khaled , Elrashedy Asmaa Ahmed , Abdelnaby Ramy , Elsayed Mohamed , Gaber Dina Elsayed 
Published: February 2024

Abstract
Background
Parkinson's disease (PD) is a chronic progressive neurodegenerative disabling disease and involves about 1–3% of the worldwide population over the age of 60. A significant prevalence of psychopathological symptoms has been recorded as most patients with PD developed over their disease course neuropsychiatric symptoms such as depression, anxiety, sleep disorders, psychosis, and cognitive and behavioral abnormalities. These non-motor symptoms, which could appear decades before motor ones, become disturbing symptoms during the later phases of the disease. Hence, the current research aims to study depressive symptoms in Parkinson's disease patients. Thirty-six patients with Parkinson’s disease aged from 40 to 65 years (20 males and 16 females) and 36 age and sex-matched controls (19 males and 17 females) were included in the study. Unified Parkinson’s Disease Rating Scale (UPDRS), Hoehn and Yahr scale, Schwab and England’s scale, Mini-Mental State Examination, Cognitive Ability Screening Instrument, and Hamilton Depression Rating Scale were applied to assess depression in both groups.

Results
Patients were 20 males and 16 females (mean age 52.44 ± 7.45), mean duration of Parkinsonism was 3.88 years. The mean value for Hoehn and Yahr scale was 1.97 ± 1.42, for UPDRS T was 42.41 ± 20.91 and Schwab England's scale was 74.77 ± 17.78. Concerning cognition, MMSE was significantly lower among patients 25.33 ± 3.63, than in the control group and CAS total was significantly lower in patients (16 ± 71.35) than in the control group 9.81 ± 84.62.

Conclusion
Depressive symptoms are widespread in Parkinson's disease. Depression should be strictly determined and addressed, particularly in patients with more advanced cognitive impairment who are at a higher risk of developing or worsening depression.
The future of minimally invasive spine surgery in low-income Latin American countries
Authors: Santos Daniel Encarnacion , Bozkurt Ismail , Nurmukhametov Renat , Dosanov Medet , Volovish Alexander , Chmutin Gennady , Sierra Ariel Tapia , Eneliz Brenda , Bernard Edwin , Nakry Phon , Scalia Gianluca , Chaurasia Bipin 
Published: February 2024

AbstractTreatment of spinal disorders can be managed conservatively or surgically. With the trend toward minimalistic approaches, minimally invasive spinal surgery (MISS) has gained much more importance over the last decade. Its use along with the required training has tremendously increased in developed countries. However, the availability of MISS today is uneven in different regions due to the development and availability of technology, as well as the level of training and qualifications of surgeons who are able to perform such operations on the spine. The purpose of this article is to analyze the prospects for minimally invasive spine surgery in Latin America in comparison with higher income countries.
Indolent Behavior of Malignant Bethesda III Nodules Compared to Bethesda V/VI Nodules
Authors: Endo Mayumi , Peng Jing , Nabhan Fadi A , Brock Pamela , Azaryan Irina , Long Clarine , Ryan Laura E , Ringel Matthew D , Sipos Jennifer A 
Published: February 2024

Abstract

Background
The Bethesda system classifies all fine-needle aspiration specimens into 1 of 6 categories. We speculated that cancers within each Bethesda category would have distinct clinical behavior.

Methods
This is a retrospective analysis of patients from a single academic medical center with a histologic diagnosis of thyroid cancer who had an initial diagnosis of Bethesda III, IV, V, or VI cytology.

Results
A total of 556 cases were included, with 87 cases of Bethesda III, 109 cases of IV, 120 cases of V, and 240 cases of VI. Bethesda III showed similarities with V/VI compared to IV with a predominance of papillary thyroid cancer. The interval from diagnosis to surgery was longer in Bethesda III compared to Bethesda V/VI (median 78 vs 41 days, P &lt; .001) (Fig. 1). Yet, patients with Bethesda III had a higher probability of achieving remission (62% vs 46%, P &lt; .03), a lower possibility of recurrence (8% vs 24%, P &lt; .001), and a shorter interval to achieve remission (median 1218 vs 1682 days, P = .02) compared to Bethesda V/VI, which did not change after adjusting for age, sex, radioactive iodine therapy, mode of surgery, and tumor size. More than 70% of Bethesda III that later presented with recurrence had T3/T4 disease or distant metastasis.

Conclusion
Cancers with Bethesda III cytology had a less aggressive clinical phenotype with better prognosis compared to V/VI despite histological similarities. The time to remission was shorter in Bethesda III despite a longer interval between diagnosis and surgery. The initial cytological diagnosis may guide management.
Expression and Prognostic Relevance of PD-1, PD-L1, and CTLA-4 Immune Checkpoints in Adrenocortical Carcinoma
Authors: Landwehr Laura-Sophie , Altieri Barbara , Sbiera Iuliu , Remde Hanna , Kircher Stefan , Olabe Julie , Sbiera Silviu , Kroiss Matthias , Fassnacht Martin 
Published: February 2024

Abstract

Context
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with poor prognosis in advanced stages. While therapies targeting the checkpoint molecules programmed cell death 1 (PD-1), its ligand PD-L1, and the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) have revolutionized treatment in many cancers, the results in ACCs were heterogeneous.

Objective
Their expression in ACC has not been systematically studied and might explain the variable response to immune checkpoint inhibitors.

Methods
The expression of PD-1, PD-L1 and CTLA-4 was examined in 162 tumor samples from 122 patients with ACC by immunohistochemistry (threshold of &gt;1%) and correlated with tumoral T lymphocyte infiltration and clinical endpoints. Finally, univariate and multivariate analyses of progression-free and overall survival were performed.

Results
PD-1 and PD-L1 were expressed in 26.5% and 24.7% of samples, respectively, with low expression in most tumor samples (median positive cells: 2.1% and 21.7%). In contrast, CTLA-4 expression was observed in 52.5% of ACC with a median of 38.4% positive cells. Positive PD-1 expression was associated with longer progression-free survival (HR 0.50, 95% CI 0.25-0.98, P = .04) even after considering prognostic factors. In contrast, PD-L1 and CTLA-4 did not correlate with clinical outcome. Additionally, PD-1 and PD-L1 expression correlated significantly with the amount of CD3+, CD4+, FoxP3+, and CD8+ T cells.

Conclusion
The heterogeneous expression of PD1, PD-L1, and CTLA-4 in this large series of well-annotated ACC samples might explain the heterogeneous results of the immunotherapies in advanced ACC. In addition, PD-1 expression is a strong prognostic biomarker that can easily be applied in routine clinical care and histopathological assessment.
Outcomes of Cytologically Indeterminate Thyroid Nodules Managed With Genomic Sequencing Classifier
Authors: Ahmadi Sara , Kotwal Anupam , Bikas Athanasios , Xiang Pingping , Goldner Whitney , Patel Anery , Hughes Elena G , Longstaff Xochitl , Yeh Michael W , Livhits Masha J 
Published: February 2024

Abstract

Context
Molecular testing can refine the risk of malignancy in thyroid nodules with indeterminate cytology to decrease unnecessary diagnostic surgery.

Objective
This study was performed to evaluate the outcomes of cytologically indeterminate thyroid nodules managed with Afirma genomic sequencing classifier (GSC) testing.

Methods
Adult patients who underwent a biopsy at 3 major academic centers between July 2017 and June 2021 with Bethesda III or IV cytology were included. All patients had surgery or minimum follow-up of 1 year ultrasound surveillance. The primary outcomes were the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of GSC in Bethesda III and IV nodules.

Results
The median nodule size of the 834 indeterminate nodules was 2.1 cm and the median follow-up was 23 months. GSC sensitivity, specificity, PPV, and NPV across all institutions were 95%, 81%, 50%, and 99% for Bethesda III nodules and 94%, 82%, 65%, and 98% for Bethesda IV nodules, respectively. The overall false-negative rate was 2%. The NPV of GSC in thyroid nodules with oncocytic predominance was 100% in Bethesda III nodules and 98% in Bethesda IV nodules. However, the PPV of oncocytic nodules was low (17% in Bethesda III nodules and 45% in Bethesda IV nodules). Only 22% of thyroid nodules with benign GSC results grew during surveillance.

Conclusion
GSC is a key tool for managing patients with indeterminate cytology, including the higher-risk Bethesda IV category. GSC-benign thyroid nodules can be observed similarly to thyroid nodules with benign cytology.
Emerging insights into CP110 removal during early steps of ciliogenesis
Authors: Xie Shuwei , Naslavsky Naava , Caplan Steve 
Published: February 2024

ABSTRACT
The primary cilium is an antenna-like projection from the plasma membrane that serves as a sensor of the extracellular environment and a crucial signaling hub. Primary cilia are generated in most mammalian cells, and their physiological significance is highlighted by the large number of severe developmental disorders or ciliopathies that occur when primary ciliogenesis is impaired. Primary ciliogenesis is a tightly regulated process, and a central early regulatory step is the removal of a key mother centriole capping protein, CP110 (also known as CCP110). This uncapping allows vesicles docked on the distal appendages of the mother centriole to fuse to form a ciliary vesicle, which is bent into a ciliary sheath as the microtubule-based axoneme grows and extends from the mother centriole. When the mother centriole migrates toward the plasma membrane, the ciliary sheath fuses with the plasma membrane to form the primary cilium. In this Review, we outline key early steps of primary ciliogenesis, focusing on several novel mechanisms for removal of CP110. We also highlight examples of ciliopathies caused by genetic variants that encode key proteins involved in the early steps of ciliogenesis.
Low prevalence of scabies and impetigo in Dakar/Senegal: A cluster-randomised, cross-sectional survey
Authors: Hansmann Andreas , Wamba Lékémo Genevia , Fomba Chiaka , Kaddoura Jade , Toure Ramatoullaye , Diop Assane , Ndiaye Maodo , Chosidow Olivier , Marks Michael , Ly Fatimata 
Published: February 2024

Background
Scabies, a parasitic infection caused by Sarcoptes scabiei var. hominis, is a public health problem with significant morbidity worldwide, particularly in low-resource countries. Impetigo, a complication of scabies infection, is a risk factor for sepsis, glomerulonephritis and possibly acute rheumatic fever. Currently, the majority of epidemiological data has been collected in rural populations in the Pacific with limited applicability to urban populations in sub-Saharan Africa, where scabies is also believed to be a problem. To inform future public health programs, more reliable information about the burden of disease is required.

Methodology/Principal findings
In July/August 2022, we conducted a cross sectional, cluster-randomised, household survey in Pikine/Dakar using the ‘International Association for the Control of Scabies (IACS)’ criteria to diagnose scabies and impetigo. All participants underwent a standardised clinical examination by post-graduate dermatology students. For those diagnosed with scabies, an age-adapted ‘Dermatology Life Quality Index (DLQI)’ questionnaire was filled. We recruited and examined 1697 participants to detect 27 cases of scabies (prevalence: 1.6%, 95% CI 0.8–3.2), mostly in school aged children. Ten participants suffered from impetigo (prevalence: 0.6%, 95% CI 0.3–1.3), 5 of which were dually infected with scabies. Risk factors for scabies infection were young age, male gender and Koranic school attendance. Of those found to have scabies, in 7 out of 22 cases (31.8%) it had a large effect on their lives according to the DLQI questionnaires filled.

Conclusions/Significance
This study adds to the mapping of the burden of scabies across Africa to support public health action. With a low prevalence of scabies that is concentrated amongst poor households and children attending Koranic schools, a focused public health approach targeting Koranic schools and poor households seems to be most appropriate in this community.
Changes in the place of death before and during the COVID-19 pandemic in Japan
Authors: Shibata Masashi , Otsuka Yuki , Hagiya Hideharu , Koyama Toshihiro , Kashiwagi Hideyuki , Otsuka Fumio 
Published: February 2024

Background
In the global aging, the coronavirus disease 2019 (COVID-19) pandemic may have affected the place of death (PoD) in Japan, where hospital deaths have dominated for decades. We analyzed the PoD trends before and during the COVID-19 pandemic in Japan.

Methods
This nationwide observational study used vital statistics based on death certificates from Japan between 1951 and 2021. The proportion of PoD; deaths at home, hospitals, and nursing homes; and annual percentage change (APC) were estimated using joinpoint regression analysis. Analyses were stratified by age groups and causes of death.

Results
After 2019, home deaths exhibited upward trends, while hospital death turned into downward trends. By age, no significant trend change was seen in the 0–19 age group, while hospital deaths decreased in the 20–64 age group in 2019. The trend change in home death in the ≥65 age group significantly increased since 2019 with an APC of 12.3% (95% confidence interval [CI]: 9.0 to 15.7), while their hospital death trends decreased by −4.0% (95% CI: −4.9 to −3.1) in 2019−2021. By cause of death, home death due to cancer and the old age increased since 2019 with an APC of 29.3% (95% CI: 25.4 to 33.2) and 8.8% (95% CI: 5.5 to 12.2), respectively.

Conclusion
PoD has shifted from hospital to home during the COVID-19 pandemic in Japan. The majority of whom were older population with cancer or old age.
Extraction of pectin from jelly fig shell using microwave heating extraction: pectin physicochemical properties and antioxidant activities
Authors: Tsai Shu-Hsien , Fan Chih-Hsuan , Chung Cheng-Pei , Lu Shih-Ting , Lee Ming-Yi 
Published: February 2024

Abstract
Jelly fig is a crop of high economic value; however, the processing by-product of jelly fig, “jelly fig shell”, is not well utilized. In this study, jelly fig shell pectin was extracted through the microwave extraction technique. Then, galacturonic acid content, degree of esterification, molecular weight, functional group properties, and antioxidant activity were determined. The highest pectin yield (21.6 ± 0.1 %) was obtained at 200 mM citric acid and microwave power of 800 W, with extraction time of 4 min. The content of galacturonic acid in pectin was greater than 65 %, which meets the specifications of food-grade pectin. In terms of antioxidant ability, the IC50 of 2,2-diphenylpicrylhydrazyl (DPPH) free radical scavenging rate of jelly fig shell pectin was 175.1 μg/mL. These results suggest that, comparing to the extracted jelly fig seed pectin, jelly fig shell has stable quality under more desirable extraction conditions, and has better physicochemical properties.