bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-calcitonin gene-related peptide monoclonal antibodies for the treatment of vestibular migraine: A prospective observational cohort study
Authors: Russo Cinzia Valeria , Saccà Francesco , Braca Simone , Sansone Mattia , Miele Angelo , Stornaiuolo Antonio , De Simone Roberto 
Published: March 2023

Background Vestibular migraine is considered the most common cause of recurrent vertigo for which specific treatments are missing. Monoclonal antibodies against calcitonin gene-related peptide,, are effective in preventing migraine. Since CGRP is also detected in human cochlear and vestibular organs it may also play a role in vestibular physiology. Methods This is a prospective observational cohort study, aiming at evaluating the efficacy of erenumab, fremanezumab or galcanezumab for the treatment of fifty vestibular migraine patients. We assessed mean monthly days with headache and dizziness/vestibular symptoms, pain intensity and migraine-related clinical burden occurring for 18 months. Results Response to treatment was excellent as 45 (90%) patients had at least a 50% reduction in vertigo frequency, 43 (86%) had at least a 50% reduction in headache frequency, and 40 (80%) a MIDAS reduction of at least 50%. Overall, 39 (78%) patients had a concomitant reduction of all three parameters. Mean monthly days with dizziness/vestibular symptoms showed an overall significant decrease from a mean of 10.3 ± 1.9 at baseline to 0.8 ± 0.3 days, difference 9.5 (CI 95% 3.6, 15.4; p < 0.001) after twelve months. Conclusion We show that anti-CGRP mAbs may be effective in the treatment of Vestibular Migraine. Their use should be encouraged early in the disease course to allow for a better symptom control and quality of life improvement.
Inhibiting PAC1 receptor internalization and endosomal ERK pathway activation may ameliorate hyperalgesia in a chronic migraine rat model
Authors: Zhang Lily , Zhou Yanjie , Wang Yajuan , Yang Liu , Wang Yue , Shan Zhengming , Liang Jingjing , Xiao Zheman 
Published: March 2023

Background Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multipotent neuropeptide widely distributed in the trigeminovascular system (TVS) and higher brain regions. At present, the underlying mechanism of PACAP/PACAP type1 (PAC1) receptor in migraine generation remains unclear. Methods The rat model of chronic migraine (CM) was established by repeated intraperitoneal injection of nitroglycerin (NTG). Von Frey filaments and hot plate tests were used to measure the mechanical and thermal thresholds. The expression levels of c-Fos, calcitonin gene-related peptide (CGRP), PACAP, PAC1, protein kinase A (PKA) and phosphorylated extracellular signal-regulated kinase (ERK) were assessed by western blotting or immunofluorescence staining. The internalization of PAC1 receptor was visualized by fluorescence microscope and laser scanning confocal microscope. Results The results showed that c-Fos and CGRP expression significantly increased after repeated administrations of NTG or PACAP. Pitstop2 notably improved hyperalgesia in CM rats, while PACAP6–38 offered no benefit. In addition, PACAP-induced PAC1 receptor internalization, PKA and ERK pathways activation were blocked by Pitstop2 instead of PACAP6–38. Conclusions Our results demonstrate that inhibition of PAC1 receptor internalization could effectively improve allodynia in CM rats by restraining ERK signaling pathway activation in a chronic migraine rat model. Modulation of receptor internalization may be a novel perspective to explore specific mechanisms of PACAP signaling activation in the trigeminal vascular system.
Functional properties and characterization of maize starch films blended with chitosan
Authors: Hao Yanling , Cheng Long , Song Xiaoshuang , Gao Qiqi 
Published: March 2023

The preparation of biodegradable composite films from blending chitosan in maize starch via solution casting was explored and the effect of the ratio of chitosan/starch on the physicochemical, mechanical properties and antimicrobial activity of the films was investigated. The interaction through hydrogen bonding between starch molecules and chitosan and the reduction of crystallinity in blend films were revealed in FTIR and XRD results. The blend films with incorporation of proper amounts of chitosan to a maize starch matrix displayed an enhancement in tensile properties and water vapor barrier performance, an improvement in rigidity and antimicrobial activity accompanied by higher transparency. The film with 1/3 of chitosan/starch ratio appeared homogeneous structure, 21.54 ± 0.78 MPa of tensile strength and (2.81 ± 0.26)×10−10 g·m−1·s−1·Pa−1 of water vapor permeability which were 1.52 times higher and 60.9% lower than those of starch film, respectively. The deteriorated comprehensive performance of the films could be caused by excessively high chitosan content because of an incomplete miscibility between starch and chitosan. The chitosan/starch blend film possessed reasonable thermal stability and it could potentially be useful for food packaging applications.
Psychosocial determinants of pre-exposure prophylaxis use among pregnant adolescent girls and young women in Cape Town, South Africa: A qualitative study
Authors: Haribhai Sonia , Khadka Nehaa , Mvududu Rufaro , Mashele Nyiko , Bekker Linda-Gail , Gorbach Pamina , Coates Thomas J , Myer Landon , Joseph Davey Dvora Leah 
Published: March 2023

Background In South Africa, at least 7.5 million people (age ≥15 years) are living with Human Immunodeficiency Virus (HIV). In 2020, 220,000 new infections occurred, approximately one-third of which were among cisgender adolescent girls and women (age ≥15 years). The perspectives of pregnant adolescent girls and young women (AGYW) as key, targeted end-users of pre-exposure prophylaxis (PrEP) in this setting are not well known. Methods We purposively recruited participants enrolled in an ongoing cohort study at an urban antenatal clinic in Cape Town, South Africa for in-depth interviews between July–September 2020. We restricted our analysis to pregnant AGYW (age: 16–25 years) who initiated daily oral PrEP (Tenofovir/Emtricitabine) antenatally and self-reported either high PrEP persistence (≥25 days in the past 30 days and no missed PrEP collection), or low PrEP persistence and/or discontinuation (missing >5 days in the last 30 days or missed PrEP collection). The findings were organized thematically, per the adapted Health Behavior Model (2000), using Nvivo-v.1.5. Results We interviewed 18 AGYW (mean age = 22 years), at a mean of 14 weeks postpartum. Higher self-esteem and high-quality study provider-client relationships, including empathic psychosocial support, facilitated PrEP continuation. Reported barriers included unstable social structure characteristics (i.e., financial hardship) and individual factors (i.e., unintended pregnancy, parental rejection, and inadequate peer- and [non-cohabiting] partner support). Participants self-perceived a need for PrEP, feeling susceptible to non-consensual, forced sex, or considering partners’ (presumed) sexual risk-taking. Limited community awareness regarding PrEP availability and/or perceived complexity in navigating health system access to PrEP, impede continuation. Conclusions PrEP-focused healthcare access pathways for pregnant and postpartum AGYW need to be simplified. Further research is needed on health system determinants (i.e., structural barriers, provider-client interactions, and related outcomes) of oral PrEP utilization. In 2022, South Africa announced regulatory approval of long-acting PrEP options (i.e., the dapivirine ring for non-pregnant women and injectable cabotegravir, respectively); these may mitigate implementation barriers reported in this study. However, the safety and efficacy of long-acting PrEP (e.g., injectables, implants) among pregnant or breastfeeding women, specifically, remains to be confirmed in this setting.
Next generation sequencing to examine associations between vaginal washing and vaginal microbiota: A cohort study
Authors: Sabo Michelle C , Balkus Jennifer E , Richardson Barbra A , Srinivasan Sujatha , Kimani Joshua , Anzala Omu , Schwebke Jane , Fiedler Tina L , Fredricks David N , McClelland R Scott 
Published: March 2023

Background The association between vaginal washing and HIV risk may be mediated by vaginal washing-associated changes in vaginal microbiota. Methods Data from a cohort of HIV-negative US and Kenyan women enrolled in the Preventing Vaginal Infections trial were analyzed. Vaginal fluid samples and vaginal washing data were collected every 2 months for 12 months. Bacterial relative abundances were measured by broad-range 16S rRNA gene polymerase chain reaction with next generation sequencing. Generalized estimating equations were used to evaluate the association between vaginal washing and i) the Shannon Diversity Index (SDI); and ii) mean change in percent bacterial relative abundances, with application of a 10% false discovery rate (FDR). Results Participants ( N = 111) contributed 93/630 (14.8%) vaginal washing visits. Mean SDI was 0.74 points higher (95% CI 0.35, 1.14; p < 0.001) at washing visits among US participants ( N = 26). Vaginal washing was not associated with SDI in Kenyan participants ( N = 85). There were no associations between vaginal washing and vaginal bacterial relative abundances after applying the FDR. Conclusions The discordant results in Kenyan versus US women suggests the link between vaginal washing and sub-optimal vaginal microbiota may be context specific. Vaginal microbial shifts may not fully explain the association between vaginal washing and HIV acquisition.
The Cognitive Skills in Interpretation of Spatial Situations in the League of Legends game
Authors: Horbiński Tymoteusz , Zagata Krzysztof 
Published: March 2023

Background League of Legends is one of the most popular video games in the world. With the help of the new initiatives of the developers and publishers (Riot Games), professional international and local tournaments were established. Riot Games also took care of establishing regional leagues, such as LCK (League of Legends Champions Korea) or LEC (League of Legends European Championship). The best teams from each region have an annual chance to compete in October / November to become the esports world champions in LoL. Watching the tournaments such as world champions, as well as amateur streams on popular platforms (Twitch, YouTube) is now trending more and more. The fact that the game (especially spatial situations) can be observed by both experts (players of this game) and non-experts (players of other games or non-players at all) creates a field for scientific research. Intervention The authors of this article wanted to establish whether or not the League of Legends game offers gamers with different levels of knowledge of the entire game and different range of cognitive skills the same interpretation of spatial situations. Methods The research was carried out in the form of a questionnaire (offline), in which respondents were supposed to watch five short videos presenting different situations during the game. Eighty-two respondents, divided into three groups, participated in the research. The Pearson chi-square test was used for the analysis of the differences between groups. Results and Discussion As a consequence of the results of this study it may be concluded that gamers on different advancement level do not present the same level of interpretation of spatial situations in the game. The authors, using the scheme of knowledge of the point, lane, and area in the construction of video questionnaire did not focus on the game as a whole, but wanted to highlight crucial elements of the entire game.
Critical Care Pharmacist Attitudes and Perceptions of Neuromuscular Blocker Infusions in ARDS
Authors: Devlin John W. , Train Sarah E. , Burns Karen E. A. , Massaro Anthony , Wu Ting Ting , Castor Timothy , Vassaur John , Selvan Kavitha , Kress John P. , Erstad Brian L. 
Published: March 2023

Background: Current critical care pharmacist (CCP) practices and perceptions related to neuromuscular infusion (NMBI) use for acute respiratory distress syndrome (ARDS) maybe different with the COVID-19 pandemic and the publication of 2020 NMBI practice guidelines. Objective: To evaluate CCP practices and perceptions regarding NMBI use for patients with moderate-severe ARDS. Methods: We developed, tested, and electronically administered a questionnaire (7 parent-, 42 sub-questions) to 409 American College of Clinical Pharmacy (ACCP) Critical Care Practice and Research Network members in 12 geographically diverse states. The questionnaire focused on adults with moderate-severe ARDS (PaO2:FiO2<150) whose causes of dyssynchrony were addressed. Two reminders were sent at 10-day intervals. Results: Respondents [131/409 (32%)] primarily worked in a medical intensive care unit (ICU) 102 (78%). Compared to COVID-negative(-) ARDS patients, COVID positive(+) ARDS patients were twice as likely to receive a NMBI (34 ± 18 vs.16 ± 17%; P < 0.01). Respondents somewhat/strongly agreed a NMBI should be reserved until after trials of deep sedation (112, 86%) or proning (92, 81%) and that NMBI reduced barotrauma (88, 67%), dyssynchrony (87, 66%), and plateau pressure (79, 60%). Few respondents somewhat/strongly agreed that a NMBI should be initiated at ARDS onset (23, 18%) or that NMBI reduced 90-day mortality (12, 10%). Only 2/14 potential NMBI risks [paralysis awareness (101, 82%) and prolonged muscle weakness (84, 68%)] were frequently reported to be of high/very high concern. Multiple NMBI titration targets were assessed as very/extremely important including arterial pH (109, 88%), dyssynchrony (107, 86%), and PaO2: FiO2 ratio (82, 66%). Train-of-four (55, 44%) and BIS monitoring (36, 29%) were deemed less important. Preferred NMBI discontinuation criteria included absence of dysschrony (84, 69%) and use ≥48 hour (72, 59%). Conclusions and Relevance: Current critical care pharmacists believe NMBI for ARDS patients are best reserved until after trials of deep sedation or proning; unique considerations exist in COVID+ patients. Our results should be considered when ICU NMBI protocols are being developed and bedside decisions regarding NMBI use in ARDS are being formulated.
30 Years of International Climate Negotiations: Are They Still our Best Hope?
Authors: Clémençon Raymond 
Published: March 2023

30 years of international climate talks have not prevented the globe from heating up more than 1 degree Celsius over post-industrial times, nor have they kept the year 2022 from breaking new temperature and extreme weather records around the world. Although the international process has been indispensable for building the foundation to move out of the carbon age, it is now time to shift attention away from the acrimonious climate talks and treat them as a sideshow, rather than the solution to the problem. An analysis of 30 years of international climate negotiations shows that multilateral climate diplomacy years ago stopped driving countries’ action. National political opportunity structures, normative shifts, economic factors, and external events are what shape countries’ climate policies largely independent of international climate negotiations.
The 2-Window Posterolateral vs Single-Window Approach for Ankle Fracture Fixation
Authors: Herbosa Christopher G. , Leucht Philipp , Egol Kenneth A. , Tejwani Nirmal C. 
Published: March 2023

Background: The posterolateral approach to the ankle allows for reduction and fixation of the posterior and lateral malleoli through the same surgical incision. This can be accomplished via 1 or 2 surgical “windows.” The purpose of this study is to compare outcomes including wound complications following direct fixation of unstable rotational ankle fracture through the posterolateral approach using either 1 or 2 surgical windows. Methods: One hundred sixty-four patients with bi- or trimalleolar ankle fractures treated using the single-window posterolateral approach (between the peroneal tendons and the flexor hallucis longus [FHL]) or the 2-window technique (between the peroneal tendons and the FHL for posterior malleolus fixation; lateral to the peroneal tendons for fibula fixation) were reviewed for demographics, radiographic details, and clinical outcomes. We were able to review these 164 at the 3-month follow-up and a subset of 104 at a minimum of 12-month follow-up. Results: One hundred eight ankles had the single-window approach; 56 had the 2-window approach. These 2 cohorts did not differ in demographic or injury characteristics. Ankles in the 2-window group experienced a greater number of early (3 months postsurgery) wound complications (32% vs 12%, P < .01). Two-window patients had more wound complications among ankles treated later than 1 week after injury (44% vs 16%, P < .01). There was no difference in surgical site infection, with low rates in both cohorts. Single-window patients had greater plantarflexion (35 ± 10 vs 30 ± 11 degrees, P = .025) and dorsiflexion after 12 months (21 ± 10 vs 16 ± 11 degrees, P = .021). We did not find a significant difference in nerve complications for these 2 cohorts. Conclusion: In our study, we found the single-window posterolateral approach to be associated with fewer wound complications and better postoperative range of ankle motion when compared to the 2-window approach. Level of Evidence: Level III, retrospective cohort study.
Combination of D-dimer and Albumin in the Prediction of Deep Vein Thrombosis in Patients with Spontaneous Intracerebral Hemorrhage
Authors: Chen Lingli , Zhang Wanli , Liu Chunfeng 
Published: March 2023

Background and Purpose Deep venous thrombosis (DVT) makes spontaneous intracerebral hemorrhage (ICH) treatment more challenging. We aimed to determine the predictive ability of D-dimer combination with albumin for DVT in spontaneous ICH. Methods Spontaneous ICH patients were retrospectively included. Univariate and multivariate logistic regression analyses were performed. The restricted cubic spline (RCS) curve was adopted. Multivariate logistic regression analysis was further conducted to assess the predictive powers of D-dimer and albumin in different models. Besides, the incremental predictive ability of D-dimer combination with albumin was evaluated with areas under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination index (IDI). Results D-dimer was significantly higher, while albumin was considerably lower in the DVT group than in the non-DVT group [D-dimer, 0.47 (0.29, 1.08) versus 0.98 (0.48, 2.49), P < .001; albumin, 39.45 ± 7.05 versus 36.93 ± 4.77, P < .001). The multivariate logistic regression analysis showed that higher D-dimer and lower albumin were independently related to DVT after controlling confounders (D-dimer, OR = 1.061, 95% CI = 1.012–1.112, P = .013; albumin, OR = 0.934, 95% CI = 0.895–0.973, P = .001). The best cut-off value of the D-dimer was 0.40, and the albumin was 37.15. Besides, D-dimer and albumin had good predictive abilities in different models. The AUC, NRI, and IDI revealed that models that included the D-dimer combination with albumin had better predictability than those without. Conclusions D-dimer combination with albumin has a good predictability of DVT in spontaneous ICH.
CDK4/6 inhibitors in metastatic breast cancer, a comparison of toxicity and efficacy across agents in a real-world dataset
Authors: Buller William , Pallan Lalit , Chu Teresa , Khoja Leila 
Published: March 2023

Introduction CDK4/6 inhibitors (ribociclib, palbociclib and abemaciclib) are 1st line therapy in metastatic breast cancer (MBC). No comparative data exists between agents regarding toxicity or efficacy. Methods A retrospective study was performed at our tertiary referral centre evaluating patients on a CDK4/6 inhibitor for MBC between July 2017 and December 2021. Toxicity was evaluated along with variability in full blood counts and liver function over the first 12 weeks of therapy. Results Two hundred and seventeen patients were treated (palbociclib 59%, abemaciclib 25% and ribociclib 16%). 86% received the agent as 1st line therapy. Most patients were white women with a median age of 61 years (32–95) and ECOG 0/1. Twelve patients were switched to an alternative CDK4/6 inhibitor due to toxicity and two did not tolerate this. Toxicity profiles of agents were consistent with published trials. However, there was greater overlap in hepatitis, diarrhoea and bone marrow suppression. Blood results indicated a minimum of four weeks treatment before development of neutropenia. Forty percent of patients went onto have subsequent lines of therapy. The progression-free survival per agent was palbociclib 27.9 months (95% CI 23–32.5), ribociclib 29 months (95% CI 21.5–37.0) and abemaciclib 20.6 months (95% CI 15.0–26.0). The overall survival was palbociclib 38.0 months (95% CI 33.5–42.5), ribociclib 33.9 months (95% CI 26.7–41.1) and abemaciclib 27.3 months (95% CI 22.5–32.1). Conclusions Toxicity across CDK4/6 inhibitors overlaps. The optimal sequence of therapies post CDK4/6 inhibitors remains unknown but rechallenge with an alternative agent is possible.
The safety and efficacy of methylnaltrexone in pediatric oncology patients: A single center experience
Authors: Koranteng Lauren , Mauguen Audrey , Butler Miriam , Yan Shirley Qiong , Taylor Damani 
Published: March 2023

Introduction Peripherally acting μ-opioid receptor antagonists (PAMORAs) are used in the treatment of opioid induced constipation without impacting the actions of opioid analgesics. Subcutaneous methylnaltrexone was one of the first PAMORAs approved in April 2008 for the treatment of opioid induced constipation in adult patients. The safety and effectiveness of methylnaltrexone has not been established in pediatric patients. In this study, the use of subcutaneous methylnaltrexone in pediatric patients is analyzed and reviewed. The primary outcome is occurrence of a bowel movement within 24 h after methylnaltrexone (MNTX) administration and the number of bowel movements following treatment with methylnaltrexone. Secondary outcomes include safety in this patient cohort. Methods This is a retrospective study of 79 pediatric patients with opioid induced constipation. Patients were administered methylnaltrexone during their inpatient stay. Data on bowel activity after methylnaltrexone was obtained from the hospital information system. Results Out of the 79 patients who received methylnaltrexone, there were seven patients from whom data could not be analyzed. Of the 72 patients whose data was available, 38% ( N = 27) were documented as having a bowel movement, 62% ( N = 45) did not have a bowel movement. Reported adverse events were minimal with nausea ( N = 3), vomiting ( N = 1), and flatulence ( N = 6). Conclusion Methylnaltrexone appears safe in the pediatric population and produces bowel movements in more than a third of pediatric patients. It is a feasible and safe option for opioid induced constipation in pediatric patients.