bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of substitution to generic drugs and physicians’ perceived exclusivity of substitution: A cross sectional survey among physicians
Authors: Hatem Georges , Navasardyan Nare , Lahoud Elsa , Awada Sanaa , Itani Rana , Ajrouche Roula , Goossens Mathijs 
Published: June 2022

The use of generic medicines facilitate access to treatment and reduce the overall health cost. Policies promoting generic substitution take into account many components such as quality and efficacy considering health stakeholders including physicians and pharmacists and identifying factors impacting generics prescription. The current study aimed to assess the association between the perception of physicians towards generics with their sex and age and their willingness to switch to generics after initial treatment. Furthermore, it aimed to evaluate the predictors for switching brands to generics after initial treatment and perceiving the exclusivity to perform this substitution. Prescription of generics to lower medical cost was more common among younger physicians compared to those 50 years and older. Interestingly, physicians aged 40 and above were more prone to prescribe generics to patients without medical coverage, while compared to physicians younger than 30 years of age. Age was significantly associated with switching initial treatment to generics, which was 2.46 times higher for physicians older than 50 years compared to those younger than 30 years. In addition, physicians practicing more than 20 years were about 1,5 times more accepting the substitution by pharmacists after initial treatment by brand while compared to physicians practicing for less than 10 years. Strategies to increase generic substitution and promoting its acceptance among physicians should take into consideration the different significant predictors. However, Further research is required to explore more factors, predicting prescription of generics in Lebanon, such as visits by medical representatives, regulations of the hospital that the physician is practicing, which are also proven to have high influence on the prescription practice of generics.
Sleep Apnea and Postoperative Medical Complications and Health Care Expenditures Following Open Reduction and Internal Fixation of Bimalleolar Ankle Fractures
Authors: Thamer Semran B. , Lam Aaron W. , Golub Ivan J. , Magruder Matthew L. , Vakharia Rushabh M. , Aiyer Amiethab A. , Abdelgawad Amr A. 
Published: June 2022

Introduction Sleep Apnea (SA) is a common sleep disorder that increases postoperative morbidity. There is limited research on how SA influences outcomes following operative fixation of ankle fractures. Therefore, the aim of this study was to determine whether patients who undergo surgical fixation for bimalleolar ankle fractures have higher rates of medical complications and health care expenditures. Methods A retrospective review from January 1, 2005 to March 31, 2014 was conducted using the parts A and B Medicare Data from PearlDiver database. Patients with and without SA on the day of the primary open reduction and internal fixation (ORIF) of their bimalleolar ankle fractures were queried using the International Classification of Diseases, Ninth Revision codes. Welch’s t-tests were used to compare costs of care. A multivariate binomial logistic regression model was used to calculate the odds ratio (OR) of adverse events. A P-value <.001 was considered statistically significant. Results There were 20 560 patients (SA = 3150; comparison cohort = 17 410) who underwent ORIF for bimalleolar ankle fractures during the study period. Sleep apnea patients were found to have significantly higher rates and odds of 90-day medical complications (21.42% vs 7.47%, OR: 3.11, P < .0001) and 90-day costs of care ($7213.12 vs $5415.79, P < .0001). Conclusion This research demonstrates an increased risk of postoperative medical complications and health care costs among patients with SA undergoing ORIF for bimalleolar ankle fractures. Level of Evidence Therapeutic, Level IV: Retrospective
Efficacy and Safety of Posterior Long-Segment Fixation Versus Posterior Short-Segment Fixation for Kummell Disease: A Meta-Analysis
Authors: Yu Yikang , Zeng Hanbing , Guo Enpin , Tang Binbin , Fang Yuan , Wu Lianguo , Xu Chao , Peng Yi , Zhang Bin , Liu Zhen 
Published: June 2022

Purpose Posterior short-segment fixation (SSF) and long-segment fixation (LSF) are two methods for the treatment of Kummell disease, but the safety and effectiveness of these two surgical methods still lack adequate medical evidence. This study aimed to evaluate the two methods. Methods Database searches for randomized controlled trials, case-control studies, and cohort studies of posterior SSF and posterior LSF in the treatment of Kummell disease were performed. After the document quality was evaluated with the Newcastle-Ottawa Quality Assessment Scale, a meta-analysis was carried out. Results Meta-analysis revealed that the operation time and intraoperative blood loss in the LSF group were higher than those in the SSF group [MD = −18.17, 95% CI (−30.31, −6.03), z = 2.93, P = .003; MD = −82.07, 95% CI (−106.91, −57.24], z = 6.48, P < .00001). The postoperative last follow-up local kyphosis angle in the SSF group was greater than that in the LSF group (MD = 3.18, 95% CI [.56, 5.81], z = 2.38, P = .02), and there were no significant differences in perioperative complications, bone cement leakage rate, incidence of adverse events during follow-up, postoperative follow-up visual analog scale, postoperative Oswestry dysfunction index, and postoperative immediate local kyphosis angle between the two groups ( P > .05). Conclusion SSF and LSF are effective and safe for the treatment of Kummell disease. SSF can reduce the operation time and intraoperative bleeding; LSF can better maintain the long-term stability of kyphosis. The methods should be evaluated by clinicians according to the individual situation of the patients.
Endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type differ between patients with and without Helicobacter pylori infection: a retrospective observational study
Authors: Iwamuro Masaya , Kusumoto Chiaki , Nakagawa Masahiro , Matsueda Kazuhiro , Kobayashi Sayo , Yoshioka Masao , Inaba Tomoki , Toyokawa Tatsuya , Sakaguchi Chihiro , Tanaka Shouichi , Tanaka Takehiro , Okada Hiroyuki 
Published: June 2022

Abstract
Background
The endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type have not been fully investigated in relation to Helicobacter pylori infection status. We compared the morphology, color, and location of these lesions between patients with and without H. pylori infection.

Methods
We retrospectively enrolled 165 patients (180 lesions) from 10 institutions. We divided the patients into the (i) Hp group (patients with current H. pylori infection [active gastritis, n = 13] and those with past infection [inactive gastritis, n = 76]) and (ii) uninfected group (H. pylori-uninfected patients, n = 52). We compared the clinical and endoscopic features of the two groups. We also performed an analysis between (i) lesions with atrophy of the surrounding gastric mucosa (atrophy group) and (ii) lesions without atrophy of the surrounding gastric mucosa (non-atrophy group).

Results
The average age was older in the Hp group than in the uninfected group (68.1 ± 8.1 vs. 63.4 ± 8.7 years, p < 0.01). Although the difference was not statistically significant (p = 0.09), multiple lesions were observed in 9 of 89 patients (10.1%) in the Hp group and in only 1 of 52 patients (1.9%) in the uninfected group. Meanwhile, significant differences were observed in the prevalence of lesions located in the gastric fornix or cardia (uninfected group: 67.3% vs. Hp group: 38.0%, p < 0.01), with an elevated morphology (80.0% vs. 56.0%, p < 0.01), with a subepithelial-like appearance (78.2% vs. 42.0%, p < 0.01), and with a color similar to that of the peripheral mucosa (43.6% vs. 25.0%, p = 0.02). The male-to-female ratio, lesion size, and presence or absence of vascular dilatation or black pigmentation on the surface were not different between the two groups. In the analysis comparing lesions with and without mucosal atrophy, the prevalence of multiple lesions was significantly higher (p = 0.02) in the atrophy group (5/25 patients, 20.0%) than in the non-atrophy group (7/141 patients, 5.0%).

Conclusions
The endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type differ between patients with and without H. pylori infection.
Exploring patient experiences and acceptability of group vs. individual acupuncture for Cancer-related pain: a qualitative study
Authors: Oberoi Devesh , Reed Erica N. , Piedalue Katherine-Ann , Landmann Jessa , Carlson Linda E. 
Published: June 2022

Abstract
Background
Individual acupuncture (AP) is a safe and effective treatment for cancer-related pain and other symptoms in cancer survivors. However, access to individual AP is limited, and costs can be prohibitive. Group AP could be a more cost-effective alternative as it is less expensive and non-inferior to individual AP for pain relief. Despite growing evidence in favour of group AP, patient acceptability and experience of group AP in cancer patients is relatively unknown. This exploratory study sought to compare patient experiences and acceptability of group versus individual AP in cancer patients.

Methods
Semi-structured, open-ended, in-depth interviews were conducted in a subset of 11 cancer patients enrolled in a randomized non-inferiority trial of group vs. individual AP for cancer pain. Participants for this study were recruited via purposive sampling, aiming for diversity in age, sex, education, employment, cancer types, and treatment arms. Data was analyzed using inductive thematic analysis.

Results
Two major themes were identified: a) overall experience of AP treatment b) value of AP. Participants across both treatment arms acknowledged improvement in pain, quality of sleep, mood and fatigue. Participants in the group AP arm reported a significant increase in perceived social support, while participants in the individual arm valued privacy and one-on-one interaction with the acupuncturist. Although some participants in the group arm had privacy-related concerns before the commencement of the program, these concerns waned after a few AP sessions. Participants across both the treatment arms reported cordial clinician-patient relationship with the acupuncturist. Willingness to pursue AP treatment in the future was comparable across both the treatment arms and was limited by out-of-pocket costs.

Conclusion
Patient acceptability and experience of treatment in group AP was on par with individual AP. Group AP may further augment perceived social support among patients and privacy concerns, if any, subside after a few sessions.

Trial registration
ClinicalTrials.gov (NCT03641222). Registered 10 July 2018 - Retrospectively registered.
RETRACTED ARTICLE: Suppression of NF-κB signaling by ECN in an arthritic model of inflammation
Authors: Khan Amna , Zhang Li , Li Chang Hu , Khan Ashraf Ullah , Shal Bushra , Khan Adnan , Ahmad Sajjad , Din Fakhar ud , rehman Zia ur , Wang Feng , Khan Salman 
Published: June 2022

Abstract
Background
The 7β-(3-ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a sesquiterpenoid isolated from the Tussilago farfara Linneaus (Asteraceae), was evaluated against acute Carrageenan and chronic complete Freund’s adjuvant (CFA)-induced arthritis in mice.

Methods
Acute and chronic arthritis were induced by administering Carrageenan and CFA to the intraplantar surface of the mouse paw. Edema, mechanical allodynia, mechanical hyperalgesia, and thermal hyperalgesia were assessed in the paw. Similarly, histological and immunohistological parameters were assessed following arthritis induced by CFA. Antioxidants, inflammatory cytokines, and oxidative stress markers were also studied in all the treated groups.

Results
The ECN treatment significantly attenuated edema in the paw and elevated the nocifensive threshold following induction of this inflammatory model. Furthermore, ECN treatment markedly improved the arthritis index and distress symptoms, while attenuating the CFA-induced edema in the paw. ECN treatment also improved the histological parameters in the paw tissue compared to the control. At the same time, there was a significant reduction in edema and erosion in the ECN-treated group, as measured by radiographic analysis. Using the Comet’s assay, we showed that ECN treatment protected the DNA from chronic CFA-induced arthritis. Immunohistochemistry analysis showed a marked decrease in the expression level of p-JNK (phosphorylated C-Jun N-terminal kinase), NF-κB (Nuclear factor-kappa B), COX-2 (Cyclooxygenase-2), and TNF-α (Tumour necrosis factor-alpha) compared to the CFA-treated group. Biophysical analysis involving molecular docking, molecular dynamics simulations, and binding free energies of ECN were performed to explore the underlying mechanism.

Conclusion
ECN exhibited significant anti-inflammatory and anti-arthritic activity against Carrageenan and CFA-induced models.
Plasma neurofilament light and its association with all-cause mortality risk among urban middle-aged men and women
Authors: Beydoun May A. , Noren Hooten Nicole , Weiss Jordan , Beydoun Hind A. , Hossain Sharmin , Evans Michele K. , Zonderman Alan B. 
Published: June 2022

Abstract
Background
Neurofilament light chain (NfL) is released into the blood during neuronal damage. NfL is linked to mortality in neurological disorders, remaining unexplored in population studies. We investigated whether initial (v1) and annualized change (δ) in plasma NfL can predict all-cause mortality in middle-aged dementia-free urban adults.

Methods
Longitudinal data were from 694 participants in the Healthy Aging in Neighborhoods of Diversity Across the Life Span study (HANDLS, mean agev1: 47.8 years, 42% male, 55.8% African American). Plasma NfL was measured prospectively at three visits. Analyses included Cox proportional hazards models for all-cause mortality risk and 4-way decomposition testing for interaction and mediation.

Results
Unlike men, women exhibited a direct association between δNfL (above vs. below median) and all-cause mortality risk in both the minimally (HR = 3.91, 95% CI 1.10–13.9, p = 0.036) and fully adjusted models (HR = 4.92, 95% CI 1.26–19.2, p = 0.022), and for δNfL (per unit increase) in the full model (HR = 1.65, 95% CI 1.04–2.61, p = 0.034). In both models, and among women, 1 standard deviation of NfLv1 was associated with an increased all-cause mortality risk (reduced model: HR = 2.01, 95% CI 1.24–3.25, p = 0.005; full model: HR = 1.75, 95% CI 1.02–2.98, p = 0.041). Only few interactions were detected for cardio-metabolic risk factors. Notably, NfLv1 was shown to be a better prognostic indicator at normal hsCRP values among women, while HbA1c and δNfL interacted synergistically to determine mortality risk, overall.

Conclusions
These findings indicate that plasma NfL levels at baseline and over time can predict all-cause mortality in women and interacts with hsCRP and HbA1c to predict that risk.
Alert sign and symptoms for the early diagnosis of pulmonary tuberculosis: analysis of patients followed by a tertiary pediatric hospital
Authors: Farina Elisa , D’Amore Carmen , Lancella Laura , Boccuzzi Elena , Ciofi degli Atti Marta Luisa , Reale Antonino , Rossi Paolo , Villani Alberto , Raponi Massimiliano , Raucci Umberto 
Published: June 2022

AbstractBackgroundIntercepting earlier suspected TB (Tuberculosis) cases clinically is necessary to reduce TB incidence, so we described signs and symptoms of retrospective cases of pulmonary TB and tried to evaluate which could be early warning signs.MethodsWe conducted a retrospective descriptive study of pulmonary TB cases in children in years 2005–2017; in years 2018–2020 we conducted a cohort prospective study enrolling patients < 18 years accessed to Emergency Department (ED) with signs/symptoms suggestive of pulmonary TB.ResultsIn the retrospective analysis, 226 patients with pulmonary TB were studied. The most frequently described items were contact history (53.5%) and having parents from countries at risk (60.2%). Cough was referred in 49.5% of patients at onset, fever in 46%; these symptoms were persistent (lasting ≥ 10 days) in about 20%. Lymphadenopathy is described in 15.9%. The prospective study enrolled 85 patients of whom 14 (16.5%) were confirmed to be TB patients and 71 (83.5%) were non-TB cases. Lymphadenopathy and contact history were the most correlated variables. Fever and cough lasting ≥ 10 days were less frequently described in TB cases compared to non-TB patients (p < 0.05).ConclusionsIn low TB endemic countries, pulmonary TB at onset is characterized by different symptoms, i.e. persistent fever and cough are less described, while more relevant are contact history and lymphadenopathy. It was not possible to create a score because signs/symptoms usually suggestive of pulmonary TB (considered in the questionnaire) were not significant risk factors in our reality, a low TB country.
Clinical characteristics and genetic testing outcome of suspected hereditary peripheral nerve sheath tumours in a tertiary cancer institution in Singapore
Authors: Loh Jerold , Ong Pei Yi , Goh Denise Li Meng , Puhaindran Mark E. , Vellayappan Balamurugan A. , Ow Samuel Guan Wei , Chan Gloria , Lee Soo-Chin 
Published: June 2022

Abstract
Background
Peripheral Nerve Sheath Tumors (PNST) are a diverse group of mostly benign tumours uncommon in the general population. About 5–10% of PNSTs are hereditary, predominantly arising from germline variants in NF1, NF2, SMARCB1, or LZTR1 gene.

Methods
We reviewed the clinical characteristics and genetic testing results of patients referred to the NCIS Adult Cancer Genetics Clinic for suspected hereditary PNST.

Results
3,001 patients suspected to have various hereditary cancer syndromes were evaluated between year 2000 to March 2021. 13 (0.4%) were clinically diagnosed to have hereditary PNSTs. The majority were male (54%), with a median age at presentation to the genetics clinic of 29 years (range 19–48). 11/13 (85%) patients had multiple PNSTs, 12/13 (92%) had young onset PNSTs, 5/13 (38.5%) had personal and family history of PNST. 11/13 patients (85%) had clinical features of neurofibromatosis type 1 (NF1) including one patient who also fulfilled clinical criteria of neurofibromatosis type 2 (NF2); 2/13 (14%) had multiple schwannomas. Four patients underwent multi-gene panel testing, including one patient with clinical NF1, one patient who met both clinical NF1 and NF2 criteria, and two patients with multiple schwannomas. The patient with clinical features of NF1 was heterozygous for a pathogenic c. 2033dup variant in the NF1 gene. The patient with both NF1/NF2 features was heterozygous for a novel c.732 T > A nonsense variant in the NF2 gene. The two patients with multiple schwannomas were heterozygous for a pathogenic/likely pathogenic variant in the LZTR1 gene and are the first LZTR1-positive schwannomatosis patients reported in Asia.

Conclusion
Hereditary PNSTs are rare referrals to an adult cancer genetics clinic. NF1 is the most common PNST seen. LZTR1 variants may be the underlying cause in Asian patients with multiple schwannomatosis.
Mendelian randomization analysis of 37 clinical factors and coronary artery disease in East Asian and European populations
Authors: Wang Kai , Shi Xian , Zhu Ziwei , Hao Xingjie , Chen Liangkai , Cheng Shanshan , Foo Roger S. Y. , Wang Chaolong 
Published: June 2022

AbstractBackgroundCoronary artery disease (CAD) remains the leading cause of mortality worldwide despite enormous efforts devoted to its prevention and treatment. While many genetic loci have been identified to associate with CAD, the intermediate causal risk factors and etiology have not been fully understood. This study assesses the causal effects of 37 heritable clinical factors on CAD in East Asian and European populations.MethodsWe collected genome-wide association summary statistics of 37 clinical factors from the Biobank Japan (42,793 to 191,764 participants) and the UK Biobank (314,658 to 442,817 participants), paired with summary statistics of CAD from East Asians (29,319 cases and 183,134 controls) and Europeans (91,753 cases and 311,344 controls). These clinical factors covered 12 cardiometabolic traits, 13 hematological indices, 7 hepatological and 3 renal function indices, and 2 serum electrolyte indices. We performed univariable and multivariable Mendelian randomization (MR) analyses in East Asians and Europeans separately, followed by meta-analysis.ResultsUnivariable MR analyses identified reliable causal evidence (P< 0.05/37) of 10 cardiometabolic traits (height, body mass index [BMI], blood pressure, glycemic and lipid traits) and 4 other clinical factors related to red blood cells (red blood cell count [RBC], hemoglobin, hematocrit) and uric acid (UA). Interestingly, while generally consistent, we identified population heterogeneity in the causal effects of BMI and UA, with higher effect sizes in East Asians than those in Europeans. After adjusting for cardiometabolic factors in multivariable MR analysis, red blood cell traits (RBC, meta-analysis odds ratio 1.07 per standard deviation increase, 95% confidence interval 1.02–1.13; hemoglobin, 1.10, 1.03–1.16; hematocrit, 1.10, 1.04–1.17) remained significant (P< 0.05), while UA showed an independent causal effect in East Asians only (1.12, 1.06–1.19,P= 3.26×10−5).ConclusionsWe confirmed the causal effects of 10 cardiometabolic traits on CAD and identified causal risk effects of RBC, hemoglobin, hematocrit, and UA independent of traditional cardiometabolic factors. We found no causal effects for 23 clinical factors, despite their reported epidemiological associations. Our findings suggest the physiology of red blood cells and the level of UA as potential intervention targets for the prevention of CAD.
Therapeutic effects of intranasal tocotrienol-rich fraction on rhinitis symptoms in platelet-activating factor induced allergic rhinitis
Authors: Teo Cheryl Wei Ling , Png Stephanie Jia Ying , Ung Yee Wei , Yap Wei Ney 
Published: June 2022

Abstract
Background
Platelet-activating factor (PAF) has been suggested to be a potent inflammatory mediator in Allergic rhinitis (AR) pathogenesis. Vitamin E, an essential nutrient that comprises tocopherol and tocotrienol, is known as a potential therapeutic agent for airway allergic inflammation. This study aimed to investigate the beneficial effects of intranasal Tocotrienol-rich fraction (TRF) on PAF-induced AR in a rat model.

Methods
Sprague Dawley rats were randomly assigned into 3 groups: Control, PAF-induced AR and PAF-induced AR with TRF treatment. To induce AR, 50 μl of 16 μg/ml PAF was nasally instilled into each nostril. From day 1 to 7 after AR induction, 10 μl of 16 μg/μl TRF was delivered intranasally to the TRF treatment group. Complete upper skulls were collected for histopathological evaluation on day 8.

Results
The average severity scores of AR were significantly higher in the PAF-induced AR rats compared to both control and PAF-induced AR with TRF treatment. The histologic examination of the nasal structures showed moderate degree of inflammation and polymorphonuclear cells infiltration in the lamina propria, mucosa damage and vascular congestion in the PAF-induced AR rats. TRF was able to ameliorate the AR symptoms by restoring the nasal structures back to normal. H&E staining demonstrated a statistically significant benefit upon TRF treatment, where minimal degree of inflammation, and a reduction in the infiltration of polymorphonuclear cells, mucosa damage and vascular congestion were observed.

Conclusion
TRF exhibited symptomatic relief action in AR potentially due to its antioxidant, anti-inflammatory and anti-allergic properties.