bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence of Invasive and Noninvasive Pneumococcal Pneumonia Hospitalizations in People Aged ≥50 Years: Assessing Variability Across Denmark and Spain
Authors: López-Lacort Mónica , Amini Marzyeh , Emborg Hanne-Dorthe , Nielsen Jens , McDonald Scott A , Valentiner-Branth Palle , Díez-Domingo Javier , Orrico-Sánchez Alejandro
Published: March 2024

Determining pneumococcal pneumonia (PP) burden in the elderly population is challenging due to limited data on invasive PP (IPP) and, in particular, noninvasive PP (NIPP) incidence. Using retrospective cohorts of adults aged ≥50 years in Denmark (2 782 303) and the Valencia region, Spain (2 283 344), we found higher IPP hospitalization rates in Denmark than Valencia (18.3 vs 9/100 000 person-years [PY], respectively). Conversely, NIPP hospitalization rates were higher in Valencia (48.2 vs 7.2/100 000 PY). IPP and NIPP rates increased with age and comorbidities in both regions, with variations by sex and case characteristics (eg, complications, mortality). The burden of PP in adults is substantial, yet its true magnitude remains elusive. Discrepancies in clinical practices impede international comparisons; for instance, Valencia employed a higher frequency of urinary antigen tests compared to Denmark. Additionally, coding practices and prehospital antibiotic utilization may further influence these variations. These findings could guide policymakers and enhance the understanding of international disparities in disease burden assessments.
Risks of incident major osteoporotic fractures following SARS-CoV-2 infection among older individuals: a population-based cohort study in Hong Kong
Authors: Lui David T W , Xiong Xi , Cheung Ching-Lung , Lai Francisco T T , Li Xue , Wan Eric Y F , Chui Celine S L , Chan Esther W Y , Cheng Franco W T , Chung Matthew S H , Au Ivan C H , Lee Chi-Ho , Ip Tai-Pang , Woo Yu-Cho , Tan Kathryn C B , Wong Carlos K H , Wong Ian C K
Published: March 2024

Population-based epidemiological studies on post-acute phase coronavirus 2019 (COVID-19)-related fractures in older adults are lacking. This study aims to examine the risk of incident major osteoporotic fractures following SARS-CoV-2 infection among individuals aged ≥50, compared to individuals without COVID-19. It was a retrospective, propensity-score matched, population-based cohort study of COVID-19 patients and non-COVID individuals identified from the electronic database of the Hong Kong Hospital Authority from January 2020 to March 2022. The primary outcome was a composite of major osteoporotic fractures (hip, clinical vertebral, and upper limb). COVID-19 patients were 1:1 matched to controls using propensity-score according to age, sex, vaccination status, medical comorbidities and baseline medications. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. A total of 429 459 COVID-19 patients were included, 1:1 matched to non-COVID individuals. Upon median follow-up of 11 months, COVID-19 patients had higher risks of major osteoporotic fractures (5.08 vs 3.95 per 1000 persons; HR 1.22 95%CI [1.15–1.31]), hip fractures (2.71 vs 1.94; 1.33 [1.22–1.46]), clinical vertebral fractures (0.42 vs 0.31; 1.29 [1.03–1.62]), and falls (13.83 vs 10.36; 1.28 [1.23–1.33]). Subgroup analyses revealed no significant interaction. In acute (within 30 days) and post-acute phases (beyond 30 days) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we consistently observed a significant increase in fractures and falls risks. Our study demonstrated increased risk of major osteoporotic fractures after SARS-CoV-2 infection in both acute and post-acute phases in older adults, partly due to increased fall risk. Clinicians should be aware of musculoskeletal health of COVID-19 survivors.
Local application of zoledronate inhibits early bone resorption and promotes bone formation
Authors: Hsieh Ming-Kai , Wang Chi-Yun , Kao Fu-Cheng , Su Hui-Ting , Chen Mei-Feng , Tsai Tsung-Ting , Lai Po-Liang
Published: March 2024

Nonunion resulting from early bone resorption is common after bone transplantation surgery. In these patients, instability or osteoporosis causes hyperactive catabolism relative to anabolism, leading to graft resorption instead of fusion.

Systemic zoledronate administration inhibits osteoclastogenesis and is widely used to prevent osteoporosis; however, evidence on local zoledronate application is controversial due to osteoblast cytotoxicity, uncontrolled dosing regimens, and local release methods. We investigated the effects of zolendronate on osteoclastogenesis and osteogenesis and explored the corresponding signaling pathways. In vitro cytotoxicity and differentiation of MC3T3E1 cells, rat bone marrow stromal cells (BMSCs) and preosteoclasts (RAW264.7 cells) were evaluated with different zolendronate concentrations. In vivo bone regeneration ability was tested by transplanting different concentrations of zolendronate with β-tricalcium phosphate (TCP) bone substitute into rat femoral critical-sized bone defects. In vitro, zolendronate concentrations below 2.5 × 10-7 M did not compromise viability in the three cell lines and did not promote osteogenic differentiation in MC3T3E1 cells and BMSCs. In RAW264.7 cells, zoledronate inhibited extracellular regulated protein kinases and c-Jun n-terminal kinase signaling, downregulating c-Fos and NFATc1 expression, with reduced expression of fusion-related dendritic cell‑specific transmembrane protein and osteoclast-specific Ctsk and tartrate-resistant acid phosphatase (. In vivo, histological staining revealed increased osteoid formation and neovascularization and reduced fibrotic tissue with 500 μM and 2000 μM zolendronate. More osteoclasts were found in the normal saline group after 6 weeks, and sequential osteoclast formation occurred after zoledronate treatment, indicating inhibition of bone resorption during early callus formation without inhibition of late-stage bone remodeling. In vivo, soaking β-TCP artificial bone with 500 μM or 2000 μM zoledronate is a promising approach for bone regeneration, with potential applications in bone transplantation.
Evolution of intraspecific floral variation in a generalist–specialist pollination system
Authors: Leménager Marion , Clark John L , Martén-Rodríguez Silvana , Almarales-Castro Abel , Joly Simon
Published: March 2024

Intraspecific processes impact macroevolutionary patterns through individual variation, selection, and ecological specialization. According to the niche variation hypothesis, the broader ecological niche of generalist species results in an increased morphological variation among individuals either because they are constituted of diversified specialized individuals each exploiting a fraction of the species’ niche or because they are constituted of true generalist individuals that experience relaxed selection. To test this hypothesis, we surveyed the individual floral morphology of species of Antillean Gesneriaceae, a group that has transitioned between specialization for hummingbird pollination and generalization multiple times throughout its evolutionary history. We characterized the profiles of corollas using geometric morphometrics and compared the intraspecific shape variance of specialists and generalists in a phylogenetic context. We used three approaches that differently accounted for the high dimensionality of morphological traits, the ancestral reconstruction of pollination syndromes over time, and the error associated with the estimation of the intraspecific variance. Our findings provide partial support for the niche variation hypothesis. If considering the whole shape in the analysis corroborated this idea, decomposing the shape into principal components indicated that not all aspects of the corolla exhibit the same pattern of variation. Specifically, pollination generalists tend to display greater intraspecific variation than specialists in terms of tubularity, but not of curvature. Accounting for the error in the variance estimation also reduced the support for the hypothesis, suggesting that larger sample sizes may be required to reach stronger conclusions. This study emphasizes the reciprocal influence between plants and their pollinators on floral morphology at different biodiversity scales and suggests that ecological strategies of species can affect patterns of morphological variation at macroevolutionary scales.
Cooperation in public goods game does not require assortment and depends on population density
Authors: Károlyi Adél , Scheuring István
Published: March 2024

The threshold public goods game is one of the best-known models of non-linear public goods dilemmas. Cooperators and defectors typically coexist in this game when the population is assumed to follow the so-called structured deme model. In this article, we develop a dynamical model of a general N-player game in which there is no deme structure: Individuals interact with randomly chosen neighbours and selection occurs between randomly chosen pairs of individuals. We show that in the deterministic limit, the dynamics in this model leads to the same replicator dynamics as in the structured deme model, i.e., coexistence of cooperators and defectors is typical in threshold public goods game even when the population is completely well mixed. We extend the model to study the effect of density dependence and density fluctuation on the dynamics. We show analytically and numerically that decreasing population density increases the equilibrium frequency of cooperators till the fixation of this strategy, but below a critical density cooperators abruptly disappear from the population. Our numerical investigations show that weak density fluctuations enhance cooperation, while strong fluctuations suppress it.
A pilot screening project for the detection of hip dysplasia in young patients
Authors: Møse Frederik Berstad , Mohseni Shahin , Borg Tomas
Published: March 2024

Hip dysplasia in young adults is underdiagnosed and can cause pain and discomfort. Progression to osteoarthritis (OA) is common, necessitating total hip arthroplasty at an early age. When discovered early, symptomatic patients can be offered physiotherapy and/or hip-preserving surgery to alleviate pain and decrease the risk of early OA. A pilot project to screen radiograms for hip dysplasia was started across the Swedish region of Örebro Län in January 2019, comparing the incidence of dysplasia before and after initiation of the screening program. All elective conventional radiograms of the hip (age 12–44 years), requested by primary care physicians, were analyzed by consultant radiologists according to a pre-established algorithm to identify hip abnormalities. If the hip radiograms showed dysplastic changes, or other pathological signs, the radiologist advised referral to a specialized Youth Hip Clinic for further work-up and treatment. A total of 1056 radiograms were requested by clinicians during the study periods (601 and 455 during 2018 and 2020, respectively). A total of 457 trauma-related cases were excluded, resulting in 599 available for analysis (348 and 251 during 2018 and 2020, respectively). During 2018, 17 patients (4.9%) received the radiologic diagnosis of dysplasia, compared with 44 patients (17.5%) during 2020 (P < 0. 001). A three-fold increase of patients diagnosed with hip dysplasia was detected as a result of the implementation of the screening program. The advantage of screening is early referral to an orthopedic department for evaluation and consideration for physiotherapy and/or surgical intervention.
Copyright, text & data mining and the innovation dimension of generative AI
Authors: Tyagi Kalpana
Published: March 2024

The rise of Generative AI has raised many questions from the perspective of copyright. From the lens of copyright and database rights, issues revolve not only around the authorship of AI-generated outputs, but also the very process that leads to the generation of these outputs, namely the process of text and data mining (TDM). Does unauthorized TDM process infringe the economic rights of the rightholders? How does the TDM-debate transform and transmute in the age of Generative AI? Generative AI tools create works that substitute the content creators whose very work that they learn from, and successively improvise themselves with every iteration. Generative AI, thus, also presents larger policy question as they substitute the romanticized human author that sits at the centre of copyright. In addition, as Generative AI tools, such as ChatGPT, can now also crawl the web, questions thus transcend the frontiers of copyright, and touch upon innovation and competition in the market for web browsers. This research article contemplates on the foregoing issues, and makes some recommendations to create a balanced framework, whereby incentives to innovate are preserved, and the interests of the human author are suitably safeguarded in the age of TDM and Generative AI.
Rosemary essential oil potentiates the antitumour activity of 5-fluorouracil in human colorectal carcinoma cells
Authors: El Sala Amine Ali , Khawaja Ghada , Khalil Mahmoud , Salam Sherine Abdel
Published: March 2024

Objectives

Improving response rates in colorectal cancer (CRC) is an urgent clinical need. This study aimed to explore the synergistic action of Lebanese rosemary essential oil (REO) and 5-fluorouracil (5-FU) in HCT116 CRC cells.

Methods

We tested the cell viability of monotherapy and combination therapy. The combination index was calculated using CompuSyn software to evaluate drug–drug interactions and the level of synergistic cytotoxicity. We also evaluated cell migration and cytopathology. Furthermore, cell apoptosis-related proteins (i.e. Bax and Bcl-2) were measured by Western blot analysis.

Key findings

The REO/5-FU combination synergistically reduced cell viability, effectively decreased cell migration, and increased the Bax/Bcl-2 ratio in HCT116 cells. This triggered a proapoptotic morphology and initiated an apoptotic cascade in HCT116 cells, as indicated by a higher Bax/Bcl-2 ratio.

Conclusions

Our results provide evidence of the REO/5-FU combination as a better approach to improve 5-FU anticancer efficacy and allow the use of lower 5-FU doses due to the adjuvant effect of REO.
Development of pollinated and unpollinated ovules in Ginkgo biloba: unravelling the role of pollen in ovule tissue maturation
Authors: Muto Antonella , Talarico Emanuela , D’Apice Greta , Di Marzo Maurizio , Moschin Silvia , Nigris Sebastiano , Babolin Nicola , Greco Eleonora , Araniti Fabrizio , Chiappetta Adriana , Colombo Lucia , Baldan Barbara , Bruno Leonardo
Published: March 2024

In gymnosperms such as Ginkgo biloba, the arrival of pollen plays a key role in ovule development, before fertilization occurs. Accordingly, G. biloba female plants geographically isolated from male plants abort all their ovules after the pollination drop emission, which is the event that allows the ovule to capture pollen grains. To decipher the mechanism induced by pollination required to avoid ovule senescence and then abortion, we compared the transcriptomes of pollinated and unpollinated ovules at three time points after the end of the emission of pollination drop. Transcriptomic and in situ expression analyses revealed that several key genes involved in programmed cell death such as senescence and apoptosis, DNA replication, and cell cycle regulation were differentially expressed in unpollinated ovules compared to pollinated ovules. We provide evidence that the pollen captured by the pollination drop affects auxin local accumulation and might cause deregulation of key genes required for the ovule’s programmed cell death, activating both the cell cycle regulation and DNA replication genes.
Behavioral KSA Intervention Class to Boost Positive Airway Pressure Adherence Among Active Duty Military Personnel With Obstructive Sleep Apnea
Authors: Ee Juliana S , Pham Christopher K , Shaha David P , Mounts Charles W , Dogbey Godwin Y , Pogorzelski Nina
Published: March 2024

Introduction

Obstructive sleep apnea (OSA) is a treatable cause of daytime sleepiness and associated medical problems that can negatively impact soldier readiness and performance. This study examined adherence to positive airway pressure (PAP) by soldiers who were newly diagnosed with OSA and prescribed PAP therapy and participated in a Knowledge, Skills, and Attitudes (KSA) behavioral intervention class.

Materials and Methods

The KSA was a one-time, interactive 90-minute class attended by up to 10 patients per class. PAP adherence was examined using Medicare standard at 30-, 60-, 90-, and 180 days post class. The analytic sample comprised 379 active duty patients (93% men; mean age 40.21 ± 8.06) categorized into 3 groups: KSA (n = 235), did not show (DNS; n = 61), and mandatory education class (MEC; n = 83). The MEC group comprised patients from an education class in a previous year.

Results

Baseline scores on the apnea hypopnea index, body mass index, sleepiness, insomnia severity, and age were non-significant among the 3 groups. At 30 days, significantly more patients in KSA (48%) and MEC (51%) were adherent than the DNS group (16%). At 60 days, the adherence rates for the KSA, DNS, and MEC were significantly different at 39%, 22%, and 27%, respectively. At 90- and 180 days, the adherence rates among the KSA, DNS, and MEC groups did not differ significantly at 34%, 17%, and 26% (90 days) and 34%, 27%, and 25% (180 days), respectively. Consistently, more patients in KSA were adherent than those in DNS and MEC, except at 30 days. Additionally, adherence rates for KSA intervention declined more gradually over the 6 month period. The mean PAP usage on nights used was 4.6 hours that computed to a 34% non-use rate based on an optimal 7-hour/night sleep time.

Conclusion

KSA could be a behavioral intervention that enhances PAP adherence with a booster session implemented at the 90 days mark.
Tucidinostat Plus Exemestane as a Neoadjuvant in Early-Stage, Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer
Authors: Zhao Hongmeng , Li Dan , Li Qian , Zhang Bin , Xiao Chunhua , Zhao Ying , Ge Jie , Yu Yue , Jia Yumian , Guo Xiaojing , Cao Xuchen , Wang Xin
Published: March 2024

Background

To assess the efficacy and safety of tucidinostat plus exemestane as a neoadjuvant strategy in early-stage breast cancer.

Methods

This prospective, open-label, single-arm phase II trial enrolled patients with stage II-III breast cancer with hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative. Eligible patients received tucidinostat plus exemestane, and then breast-conserving surgery (BCS) or modified radical mastectomy.

Results

Among 20 enrolled patients, 3 of them achieved preoperative endocrine prognostic index (PEPI) score of 0. Additionally, complete cell cycle arrest was observed in 7, radiologic objective response rate in 10, and disease control rate in 20 patients, pathological complete response in 1 patient, and 5 patients performed BCS. Ki67 suppression from baseline to surgery was observed in 17 of patients, with the Ki67 change ratio of −73.5%. Treatment-emergent adverse event included neutropenia, leukopenia, thrombocytopenia, lymphopenia, hypoalbuminemia, aspartate aminotransferase elevation, glutamyl transpeptidase elevation, anemia, and alanine aminotransferase elevation.

Conclusions

Despite the rate of PEPI score 0 was not high, tucidinostat plus exemestane as a neoadjuvant therapy might be well tolerated and showed promising clinical responses in patients with early hormone receptor-positive, HER2-negative breast cancer. To clarify the safety and efficacy of this strategy, further investigation is warranted.

Clinical Trial Registration

ChiCTR2100046678.
Lifestyle interventions in the management of systemic sclerosis: a systematic review of the literature
Authors: Parodis Ioannis , Tsoi Alexander , Gomez Alvaro , Chow Jun Weng , Girard-Guyonvarc’h Charlotte , Stamm Tanja , Boström Carina
Published: March 2024

Objectives

We aimed to investigate the efficacy of lifestyle interventions for the management of SSc.

Methods

We searched the MEDLINE, Embase, Web of Science and CINAHL databases in June 2021. We included studies conducted on five or more patients with SSc published between 1 January 2000 and the search date evaluating lifestyle interventions, excluding systematic reviews without meta-analyses. Critical appraisal was conducted using critical appraisal tools from the Joanna Briggs Institute. Thirty-six studies were included for full-text evaluation.

Results

A total of 17 studies evaluated the effect of physical exercise alone, whereas 14 studies evaluated educational interventions for mental health management, often with physical exercise as a central component. At an aggregated level, these studies support patient education and physical exercise for the improvement of physical function, in particular hand and mouth function. Studies on diet and nutrition were few (n = 5) and pertained to gastrointestinal as well as anthropometric outcomes; these studies were insufficient to support any conclusions.

Conclusion

Physical exercise and patient education should be considered for improving physical function in patients with SSc. These interventions can be provided alongside pharmacotherapy, but there is no evidence supporting that they can be a substitute. Further research should aim at assessing the effects of reductions of harmful exposures, including tobacco smoking and alcohol, improving sleep and enhancing social relations, three hitherto underexplored facets of lifestyle in the context of SSc.
Antibacterial and antioxidant bifunctional hydrogel based on hyaluronic acid complex MoS2–dithiothreitol nanozyme for treatment of infected wounds
Authors: Lu Yongping , Kang Weiqi , Yu Yue , Liang Ling , Li Jinrong , Lu Haiying , Shi Ping , He Mingfang , Wang Yuemin , Li Jianshu , Chen Xingyu
Published: March 2024

Wound repair is a complex physiological process that often leads to bacterial infections, which significantly threaten human health. Therefore, developing wound-healing materials that promote healing and prevent bacterial infections is crucial. In this study, the coordination interaction between sulfhydryl groups on dithiothreitol (DTT) and MoS2 nanosheets is investigated to synthesize a MoS2–DTT nanozyme with photothermal properties and an improved free-radical scavenging ability. Double-bond-modified hyaluronic acid is used as a monomer and is cross-linked with a PF127-DA agent. PHMoD is prepared in coordination with MoS2-DTT as the functional component. This hydrogel exhibits antioxidant and antibacterial properties, attributed to the catalytic activity of catalase-like enzymes and photothermal effects. Under the near-infrared (NIR), it exhibits potent antibacterial effects against gram-positive (Staphylococcus aureus) and gram-negative bacteria (Escherichia coli), achieving bactericidal rates of 99.76% and 99.42%, respectively. Furthermore, the hydrogel exhibits remarkable reactive oxygen species scavenging and antioxidant capabilities, effectively countering oxidative stress in L929 cells. Remarkably, in an animal model, wounds treated with the PHMoD(2.0) and NIR laser heal the fastest, sealing completely within 10 days. These results indicate the unique biocompatibility and bifunctionality of the PHMoD, which make it a promising material for wound-healing applications.
An updated meta-analysis of the anti-methanogenic effects of monensin in beef cattle
Authors: Cooke Reinaldo F , Eloy Lidiane R , Bosco Sheila C , Lasmar Pedro V F , de Simas José M C , Leiva Tiago , de Medeiros Sergio R
Published: March 2024

Meta-analyses were performed to quantitatively summarize the effects of monensin on in vivo methane (CH4) production in beef cattle, and differentiate these outcomes according to dietary management, dose of monensin, and length of monensin supplementation. Data from 11 manuscripts describing 20 individual studies were used, and CH4 was converted to g/d when required. Studies were classified according to dose of monensin (mg/kg of diet dry matter), length of monensin supplementation prior to the last CH4 measurement, feeding management (ad libitum vs. limited-fed), and diet profile (high-forage or high-concentrate diets). Variance among studies were assessed using a χ² test of heterogeneity and calculated using I² statistics. The inclusion of monensin decreased (P < 0.01) CH4 production by 17.5 g/d when all studies were analyzed together. A moderate (P < 0.01) heterogeneity (I² = 55%) was detected for CH4 production estimates between studies; thus, meta-analyses were performed within classes. The reduction in CH4 differed (P < 0.01) according to dose of monensin, as it decreased (P < 0.01) by 25.6 g/d when the high recommended dose range was used (32 to 44 mg/kg), and tended to decrease (P ≤ 0.07) by 9.7 and 13.5 g/d when the moderate (≤31 mg/kg) and above recommended (≥45 mg/kg) doses were used, respectively. The reduction in CH4 also differed (P < 0.01) according to the length of monensin supplementation. Monensin decreased (P ≤ 0.05) CH4 production by 24.3 g/d when supplemented for <15 d, by 15.4 g/d when supplemented from 23 to 33 d, by 24.3 g/d when supplemented from 52 to 79 d, and tended to decrease (P = 0.06) CH4 production by 3.21 g/d when supplemented from 94 to 161 d. The reduction in CH4 did not differ (P = 0.37) according to diet profile, despite a 30% difference in reduction when monensin was added to high-forage (20.89 g/d) compared with high-concentrate diets (14.6 g/d). The reduction in CH4 tended to differ according to feeding management (P = 0.08), decreasing by 22.9 g/d (P < 0.01) when monensin was added to diets offered ad libitum, and by 11.5 g/d (P = 0.05) in limit-fed diets. Collectively, this study provides novel insights and further corroborates monensin as CH4 mitigation strategy in beef cattle operations. The most effective responses were observed during the first 79 d of monensin supplementation, and when monensin was included between 32 to 44 mg/kg of diet, was added to high-forage diets, and added to diets fed ad libitum.
Evaluation of a human papillomavirus vaccination training implementation in clinical and community settings across different clinical roles
Authors: Maynard Grace , Akpan Idara N , Meadows Rachel J , Fulda Kimberly G , Patel Divya A , Leidner Virginia , Taskin Tanjila , Gehr Aaron W , Lu Yan , Matches Sarah , Thompson Erika L
Published: March 2024

Improving human papillomavirus (HPV) vaccination is a national priority but uptake declined following the coronavirus pandemic. A strong predictor of HPV vaccination in the USA is a strong provider recommendation. Therefore, we developed a brief, asynchronous training on HPV vaccine recommendations in clinical and community settings as part of a multisite quality improvement initiative. This paper aims to describe the implementation and initial outcomes of the training provided. A 20-minute training on HPV vaccine bundled recommendations, motivational interviewing, and brief responses to patient concerns (Communicating about HPV vaccination to Adults and Teens; HPV CHAT) was implemented at seven safety-net clinics, two practice-based research network clinics, and nine county immunization clinics. We integrated training with clinical care teams; thus, we assessed immediate training outcomes across their different clinical roles compared to pre-training. In April–May 2022, HPV CHAT training was launched. One hundred eighty-seven people participated in the training and completed the pre-/postevaluation surveys. Knowledge about the HPV vaccine guidelines improved with notable changes in correctly reporting vaccine eligibility (P < .05). A significant change in participants’ confidence when addressing safety concerns and answering questions about the HPV vaccine (clinicians, 26.8% and 17.1%; nurses, 29.0% and 23.2%, and clinical staff, 18.2% and 37.7%) was observed. At post-test, more than 85% of clinicians and nurses reported their plan to routinely recommend the HPV vaccine. This quality improvement initiative demonstrated implementation feasibility of a brief HPV vaccine training that improved provider and clinical staff knowledge, confidence, and intention to routinely recommend HPV vaccination.
Functional Disorders of the Ileal-Anal Pouch: A Systematic Review
Authors: Church James
Published: March 2024

BACKGROUND:

The ileal pouch-anal anastomosis is a boon to patients needing proctocolectomy but maintains per anal function through anatomic and physiologic compromises. The state of pouch function is hard to define as pouch anatomy is not normal and pouch physiology is a distortion of normal defecation. Patients with pouches develop multiple symptoms; some expected, some disease related, and some the result of surgical complications. It is important to understand the cause of pouch related symptoms so that the appropriate management is offered.

OBJECTIVES:

Review pouch symptoms and discuss their likely cause. Review the literature on pouch function and dysfunction and provide clarity to the confusion.

DATA SOURCES:

PubMed and Cochrane database search using the terms “ileoanal pouch function” and “ileoanal pouch dysfunction.”

STUDY SELECTION:

A total of 553 articles from 1983 to 2023 from “ileoanal pouch function” and 178 from “ileoanal pouch dysfunction” were reviewed. Nine studies appeared under both headings. Case studies, duplicate publications, and articles concerning pouch diseases were excluded.

MAIN OUTCOME MEASURES:

Definitions of pouch function and dysfunction, methods of describing and scoring symptoms, understanding of expected changes in pouch function given the nature of the surgery.

RESULTS:

Twenty-seven studies were reviewed from the ileoanal pouch dysfunction search, and 38 from ileoanal pouch function. 3 studies tried to define normal pouch function, 10 attempted to measure pouch function, and 4 aimed at scoring pouch function. Only 3 papers addressed pouch physiology.

CONCLUSIONS:

Most studies of pouch function and dysfunction don’t consider expected changes in the physiology of defecation that follow restorative proctocolectomy. This means that most studies of pouch function produce conclusions that lack an important dimension. See symposium video.
A 15% Trichloroacetic Acid + 3% Glycolic Acid Chemical Peel Series Improves Appearance of Hand Lentigines: An Evaluator-Blinded, Split-Hand Prospective Trial
Authors: Alajmi Ali , Niaz Ghassan , Chen Christine , Lee Kachiu
Published: March 2024

BACKGROUND:

Improving the appearance of lentigines on the hands is a key component to hand rejuvenation. Soft tissue fillers revolumize hands, but do not address pigmentary changes. OBJECTIVE: This study investigated the effiacy of a 15% trichloroacetic acid (TCA) + 3% glycolic acid (GA) combination peel in improvement of appearance of hand lentigines.

METHODS

A prospective evaluator-blinded, split-hand study was performed using a 15% TCA + 3% GA peel to treat patients with hand lentigines. Subjects received a total of 3 treatments at 4-week intervals on 1 hand, with the other hand serving as an untreated control. Final photographs were taken 12 weeks after the last treatment. Two blinded board-certified dermatologists graded improvement in hand lentigines using a 5-point scale.

RESULTS

Eighteen of 20 patients completed the study (90%). The mean age was 64.4 years (SE 1.6, range 51–71). The mean pain scores were 3.8 (SE 0.4) on a 10-point scale (1 = no pain, 10 = extremely painful). Blinded evaluators correctly identified the after-treatment photographs in 16 patients (88%). Physician and patient-graded mean improvement of lentigines was significant for treated versus control hands (p < .01). No adverse events were noted.

CONCLUSION

A series of three 15% TCA + 3% GA peels are effective and safe in the treatment of hand lentigines.
Hidradenocarcinoma: A Case Series From the Scripps Clinic With a Systematic Review of the Literature
Authors: Kent Steven , Jeha George M. , Qiblawi Sultan , Malinosky Hannah , Greenway Hubert T. , Kelley Benjamin
Published: March 2024

BACKGROUND

Hidradenocarcinoma (HAC) is a rare adnexal carcinoma. To the best of the authors' knowledge, there are no published systematic reviews on HAC.

OBJECTIVE

To incorporate a case series from the authors' institution and systematically integrate reported information to provide a reference tool for optimization of diagnosis and management.

METHODS

A comprehensive MEDLINE search was conducted from database inception to 2021 using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This yielded 225 studies with 165 cases of HAC. References of included articles were also searched. In addition, 9 patients with HAC were identified from the authors' institution over the past 10 years.

RESULTS

The mean age of HAC presentation is 60 years with a slight male predilection (60%). The head and neck is the most commonly affected region. Over 36% of cases either presented with metastatic disease or went on to metastasize. The most common treatment type was wide local excision, followed by Mohs micrographic surgery.

CONCLUSION

Early detection with accurate histologic interpretation is prudent in all cases of HAC. Wide local excision is the current first-line treatment. However, Mohs micrographic surgery offers complete marginal analysis with evidence of reduced risk of metastasis and better outcomes compared with wide local excision. Currently, there are no National Comprehensive Cancer Network guidelines for the treatment of HAC, and consensus guidelines are limited to tumor and nodal metastasis staging provided by the American Joint Committee on Cancer, eighth edition. Thus, this case series and systematic review integrates important aspects of diagnosis, workup, and management of HAC.
The Effect of Pushing Rate on Foam Stability in the Tessari Method
Authors: Azmoun Sajjad , Liu Yiran , Bian Kai , Chen Anwei , Liu Shaohua
Published: March 2024

BACKGROUND

The Tessari method is commonly used in sclerotherapy for producing foam, involving 2 syringes pushed back and forth 20 times with the use of a 3-way connector. Many factors affect the foam stability which is crucial for clinical efficacy.

OBJECTIVE

This study aimed to identify the optimal pushing rate which may impact the foam stability.

MATERIALS AND METHODS

Polidocanol (POL) solution (1% and 3%) was used to make sclerosant foam via the Tessari method, with a total of 20 pushes performed at different time durations: 10, 15, 20, 25, 30, 35, and 40 seconds. The foam stability was recorded using foam half-life time (FHT), and the pushing pressure to the syringe was recorded using a self-made electric device. Both FHT and the pressure among different groups were compared respectively.

RESULTS

The FHT was decreased as pushing duration exceeding 20 seconds in POL 1% and 15 seconds in POL 3%. Both the highest FHT and pressure point were located in the 10-second group.

CONCLUSION

It is recommended to complete 20 back-and-forth passages within 10 seconds to create stable foam.
Association Between a National Behavioral Weight Management Program and Veterans Affairs Health Expenditures
Authors: Smith Valerie A. , Stechuchak Karen M. , Wong Edwin S. , Hung Anna , Dennis Paul A. , Hoerster Katherine D. , Blalock Dan V. , Raffa Susan D. , Maciejewski Matthew L.
Published: March 2024

Objective:

The association between participation in a behavioral weight intervention and health expenditures has not been well characterized. We compared Veterans Affairs (VA) expenditures of individuals participating in MOVE!, a VA behavioral weight loss program, and matched comparators 2 years before and 2 years after MOVE! initiation.

Methods:

Retrospective cohort study of Veterans who had one or more MOVE! visits in 2008–2017 who were matched contemporaneously to up to 3 comparators with overweight or obesity through sequential stratification on an array of patient characteristics, including sex. Baseline patient characteristics were compared between the two cohorts through standardized mean differences. VA expenditures in the 2 years before MOVE! initiation and 2 years after initiation were modeled using generalized estimating equations with a log link and distribution with variance proportional to the standard deviation (gamma).

Results:

MOVE! participants (n=499,696) and comparators (n=1,336,172) were well-matched, with an average age of 56, average body mass index of 35, and similar total VA expenditures in the fiscal year before MOVE! initiation ($9662 for MOVE! participants and $10,072 for comparators, standardized mean difference=−0.019). MOVE! participants had total expenditures that were statistically lower than matched comparators in the 6 months after initiation but modestly higher in the 6 months to 2 years after initiation, though differences were small in magnitude (1.0%–1.6% differences).

Conclusions:

The VA’s system-wide behavioral weight intervention did not realize meaningful short-term health care cost savings for participants.
Ambulatory Care Fragmentation and Total Health Care Costs
Authors: Kern Lisa M. , Ringel Joanna B. , Rajan Mangala , Casalino Lawrence P. , Pesko Michael F. , Pinheiro Laura C. , Colantonio Lisandro D. , Safford Monika M.
Published: March 2024

Background:

The magnitude of the relationship between ambulatory care fragmentation and subsequent total health care costs is unclear.

Objective:

To determine the association between ambulatory care fragmentation and total health care costs.

Research Design:

Longitudinal analysis of 15 years of data (2004–2018) from the national Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, linked to Medicare fee-for-service claims.

Subjects:

A total of 13,680 Medicare beneficiaries who are 65 years and older.

Measures:

We measured ambulatory care fragmentation in each calendar year, defining high fragmentation as a reversed Bice-Boxerman Index ≥0.85 and low as <0.85. We used generalized linear models to determine the association between ambulatory care fragmentation in 1 year and total Medicare expenditures (costs) in the following year, adjusting for baseline demographic and clinical characteristics, a time-varying comorbidity index, and accounting for geographic variation in reimbursement and inflation.

Results:

The average participant was 70.9 years old; approximately half (53%) were women. One-fourth (26%) of participants had high fragmentation in the first year of observation. Those participants had a median of 9 visits to 6 providers, with the most frequently seen provider accounting for 29% of visits. By contrast, participants with low fragmentation had a median of 8 visits to 3 providers, with the most frequently seen provider accounting for 50% of visits. High fragmentation was associated with $1085 more in total adjusted costs per person per year (95% CI $713 to $1457) than low fragmentation.

Conclusions:

Highly fragmented ambulatory care in 1 year is independently associated with higher total costs the following year.
Locomotion Efficiency in Children With Cerebral Palsy Experiencing Limited Gross Motor Function: Walking Versus Cycling
Authors: Dussault-Picard Cloé , Pouliot-Laforte Annie , Cherriere Claire , Houle Eloïse , Ballaz Laurent
Published: March 2024

Purpose:

This study compares cycling and walking efficiency, and energy expenditure in children with bilateral spastic cerebral palsy (CP). In children with CP, locomotion with body weight support aids such as a tricycle is a potential alternative for less exhausting movements.

Methods:

Nine children with CP traveled at comfortable speed for 6 minutes by cycling and walking. The energy expenditure index (EEI) and the percentage of the reserve heart rate (%HRR) were calculated.

Results:

The EEI was lower while cycling than walking, the traveled distance was higher while cycling than walking, and %HRR remained similar between cycling and walking.

Conclusion:

Cycling appears an efficient alternative to walking for children with CP for adapted school environments and in the community.
Mechanisms mediating arylidene-indolinones induced degradation: thoughts on “Discovery of a Drug-like, Natural Product-Inspired, DCAF11 Ligand Chemotype”
Authors: Zhong Chao , Wang Ziying , Li Zhaoyang , Li Haofeng , Xu Qianhui , Wu Wanli , Liu Cong , Fei Yiyan , Ding Yu , Lu Boxun
Published: March 2024

In the recent issue of Nature Communications (2023 Nov 30;14(1):7908), Xue et. al. reported a very interesting and significant discovery of a possible DCAF11 ligand chemotype that could be used as the “warhead” to design bifunctional compounds for targeted degradation via engaging the E3 ligase DCAF111(annotated as ref 1 hereafter). The discovery is of importance to the targeted protein degradation field and was inspired by previous reports suggesting that similar compounds may also engage the autophagosome protein LC3 for degradation and function as autophagy-tethering compounds (ATTECs)2, 3, 4, 5, 6, 7, which seem to be inconsistent with ref 1. We think that the conclusions based on these data are not necessarily mutually exclusive. After performing additional experiments and analyses, we would like to discuss some possibilities explaining such discrepancies and make a few points of clarification.
Using site-directed mutagenesis to further the understanding of insulin receptor-insulin like growth factor-1 receptor heterodimer structure
Authors: Turvey Samuel , Muench Stephen P , Issad Tarik , Fishwick Colin WG , Kearney Mark T , Simmons Katie J
Published: March 2024

Type 2 diabetes is characterised by the disruption of insulin and insulin-like growth factor (IGF) signalling. The key hubs of these signalling cascades - the Insulin receptor (IR) and Insulin-like growth factor 1 receptor (IGF1R) – are known to form functional IR-IGF1R hybrid receptors which are insulin resistant. However, the mechanisms underpinning IR-IGF1R hybrid formation are not fully understood, hindering the ability to modulate this for future therapies targeting this receptor. To pinpoint suitable sites for intervention, computational hotspot prediction was utilised to identify promising epitopes for targeting with point mutagenesis. Specific IGF1R point mutations F450A, R391A and D555A show reduced affinity of the hybrid receptor in a BRET based donor-saturation assay, confirming hybrid formation could be modulated at this interface. These data provide the basis for rational design of more effective hybrid receptor modulators, supporting the prospect of identifying a small molecule that specifically interacts with this target.
Striatal Dopamine Modulates Temporal Surprise P3a
Authors: Whitaker Grace A. , Schwartze Michael , Martin Sarah , Astudillo Aland , Silverdale Monty , El-Deredy Wael , Kotz Sonja A.
Published: March 2024

Dopamine is vital in forming mental models of “what” and “when” sensory events occur that essentially guide goal-directed behaviour. However, it remains largely unknown how variations in temporal predictability are incorporated into such mental models. A better understanding of the underlying mechanisms is important, considering dopaminergic depletion in diseases such as Parkinson’s Disease and Schizophrenia, where abnormal temporal processing is observed. Some electroencephalographic (EEG) studies indicate that noradrenergic mechanisms, as reflected in the P3b event-related potential, are modulated by temporal predictability, whereas others indicate that dopaminergic mechanisms as reflected in the P3a, underlie surprise. In this study, resting-state and task-dependent EEG was recorded from 24 healthy participants who were administered a selective D2 agonist or antagonist before they performed a pure tone auditory “oddball” task. Two oddball sequences included either partially predictable, with inter-stimulus intervals (ISIs) of 400ms/1200ms; or fully temporally predictable tones, with a consistent ISI of 600ms. Tones following 400ms ISIs were perceived as surprising, or “early”, as shown in an enhanced P3a response; tones following a 1200ms ISIs showed a much reduced P3a response (“late”). The agonist accentuated the “late” effect, demonstrating that drugs targeting D2 receptors modulate temporal prediction. These findings differentiate the role of the dopaminergic system in temporal processing and model-based auditory predictions.
Engulfment of viable neurons by reactive microglia in prion diseases
Authors: Makarava Natallia , Safadi Tarek , Mychko Olga , Pandit Narayan P. , Molesworth Kara , Baiardi Simone , Zhang Li , Parchi Piero , Baskakov Ilia V.
Published: March 2024

Microglia are recognized as the main cells in the central nervous system responsible for phagocytosis. During brain development, microglia eliminate excessive synapses and neurons, whereas in normal aging and neurodegenerative diseases, microglia are responsible for clearing protein aggregates and cell debris. The current study demonstrates that in prion disease, microglia effectively phagocytose prions or PrPScduring early preclinical stages. However, during the late preclinical stage, a critical shift occurs in microglial activity from PrPScuptake to the engulfment of neurons. This change occurs before the manifestation of clinical symptoms and is followed by a rapid accumulation of total PrPSc, suggesting a potential link to neuronal dysfunction and behavioral deficits. Surprisingly, the engulfed neurons do not show apoptotic markers, indicating that microglia are targeting viable neurons. Despite up to 40% of neurons being partially engulfed at the clinical stage, there is no significant neuronal loss, suggesting that many engulfment events are incomplete, terminated or protracted. This phenomenon of partial engulfment by reactive microglia is independent of the CD11b pathway, previously associated with phagocytosis of newborn neurons during neurodevelopment. The study establishes partial engulfment as a consistent occurrence across multiple prion-affected brain regions, various mouse-adapted strains, and different subtypes of sporadic Creutzfeldt-Jakob disease (sCJD) in humans. The current work describes a new phenomenon of partial engulfment of neurons by reactive microglia, shedding light on a novel aspect of neuronal-microglia interactions.
Repeated Binge Alcohol Drinking Leads to Reductions in Corticostriatal Theta Coherence in Female but not Male Mice
Authors: Ardinger Cherish E. , Lapish Christopher C. , Linsenbardt David N.
Published: March 2024

Decreased functional connectivity between the striatum and frontal cortex is observed in individuals with alcohol use disorder (AUD), and predicts the probability of relapse in abstinent individuals with AUD. To further our understanding of how repeated alcohol (ethanol; EtOH) consumption impacts the corticostriatal circuit, extracellular electrophysiological recordings (local field potentials; LFPs) were gathered from the nucleus accumbens (NAc) and prefrontal cortex (PFC) of C57BL/6J mice voluntarily consuming EtOH or water using a ‘drinking-in-the-dark’ (DID) procedure. Following a three-day acclimation period wherein only water access was provided during DID, mice were given 15 consecutive days of access to EtOH. Each session consisted of a 30-minute baseline period where water was available and was followed immediately by a 2-hour period where sippers containing water were replaced with new sippers containing either unsweetened 20% (v/v) EtOH (days 4-18; DID) or water (days 1-3; acclimation). Our analyses focused primarily on theta coherence during bouts of drinking, as differences in this band are associated with several behavioral markers of AUD. Both sexes displayed decreases in theta coherence during the first day of binge EtOH consumption. However, only females displayed further decreases in theta coherence on the 14thday of EtOH access. No differences in theta coherence were observed between the first and final bout on any EtOH drinking days. These results provide additional support for decreases in the functional coupling of corticostriatal circuits as a consequence of alcohol consumption and suggests that female mice are uniquely vulnerable to these effects following repeated EtOH drinking.