bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of stage shift and immunotherapy treatment on lung cancer survival outcomes
Authors: Patel Parth , Flores Raja , Alpert Naomi , Pyenson Bruce , Taioli Emanuela 
Published: June 2023

Abstract

OBJECTIVES
Non-small-cell lung cancer mortality has declined at a faster rate than incidence due to multiple factors, including changes in smoking behaviour, early detection which shifts diagnosis, and novel therapies. Limited resources require that we quantify the contribution of early detection versus novel therapies in improving lung cancer survival outcomes.

METHODS
Non-small-cell lung cancer patients from the Surveillance, Epidemiology, and End Results-Medicare data were queried and divided into: (i) stage IV diagnosed in 2015 (n = 3774) and (ii) stage I–III diagnosed in 2010–2012 (n = 15 817). Multivariable Cox-proportional hazards models were performed to assess the independent association of immunotherapy or diagnosis at stage I/II versus III with survival.

RESULTS
Patients treated with immunotherapy had significantly better survival than those who did not (HRadj: 0.49, 95% confidence interval: 0.43–0.56), as did those diagnosed at stage I/II versus stage III (HRadj: 0.36, 95% confidence interval: 0.35–0.37). Patients on immunotherapy had a 10.7-month longer survival than those who were not. Stage I/II patients had an average survival benefit of 34 months, compared to stage III. If 25%% of stage IV patients not on immunotherapy received it, there would be a gain of 22 292 person-years survival per 100 000 diagnoses. A switch of only 25% from stage III to stage I/II would correspond to 70 833 person-years survival per 100 000 diagnoses.

CONCLUSIONS
In this cohort study, earlier stage at diagnosis contributed to life expectancy by almost 3 years, while gains from immunotherapy would contribute ½ year of survival. Given the relative affordability of early detection, risk reduction through increased screening should be optimized.
Foxp3 and Bcl6 deficiency synergistically induces spontaneous development of atopic dermatitis-like skin disease
Authors: Tai Yuki , Sakaida Yuki , Kawasaki Riyo , Kanemaru Kaori , Akimoto Kazunori , Brombacher Frank , Ogawa Shuhei , Nakamura Yoshikazu , Harada Yohsuke 
Published: June 2023

Abstract
Atopic dermatitis (AD) is a common chronic skin disease caused by immune dysfunction, specifically the hyperactivation of Th2 immunity. AD is a complex disease with multiple factors contributing to its development; however, the interaction between these factors is not fully understood. In this study, we demonstrated that the conditional deletion of both the forkhead box p3 (Foxp3) and B-cell lymphoma 6 (Bcl6) genes induced the spontaneous development of AD-like skin inflammation with hyperactivation of type 2 immunity, skin barrier dysfunction, and pruritus, which were not induced by the single deletion of each gene. Furthermore, the development of AD-like skin inflammation was largely dependent on IL-4/13 signaling but not on immunoglobulin E (IgE). Interestingly, we found that the loss of Bcl6 alone increased the expression of thymic stromal lymphopoietin (TSLP) and interleukin (IL)-33 in the skin, suggesting that Bcl6 controls Th2 responses by suppressing TSLP and IL-33 expression in epithelial cells. Our results suggest that Foxp3 and Bcl6 cooperatively suppress the pathogenesis of AD. Furthermore, these results revealed an unexpected role of Bcl6 in suppressing Th2 responses in the skin.
Methane emissions and 13C composition from beef steers consuming binary C3–C4 diets
Authors: Jaramillo David M , Ruiz-Moreno Martin , Vendramini Joao M B , Sollenberger Lynn E , DiLorenzo Nicolas , Queiroz Luana M D , Santos Erick R S , Garcia Liza , Abreu Daciele S , Dubeux Jose C B 
Published: June 2023

Abstract
Improvements in forage nutritive value can reduce methane emission intensity in grazing ruminants. This study was designed to evaluate how the legume rhizoma peanut (Arachis glabrata; RP) inclusion into bahiagrass (Paspalum notatum) hay diets would affect intake and CH4 production in beef steers. We also assessed the potential to estimate the proportion of RP contribution to CH4 emissions using δ13C from enteric CH4. Twenty-five Angus-crossbred steers were randomly allocated to one of five treatments (five steers per treatment blocked by bodyweight): 1) 100% bahiagrass hay (0%RP); 2) 25% RP hay + 75% bahiagrass hay (25%RP); 3) 50% RP hay + 50% bahiagrass hay (50%RP); 4) 75% RP hay + 25% bahiagrass hay (75%RP); 5) 100% RP hay (100%RP). The study was laid out using a randomized complete block design, and the statistical model included fixed effect of treatment, and random effect of block. Methane emissions were collected using sulfur hexafluoride (SF6) technique, and apparent total tract digestibility was estimated utilizing indigestible neutral detergent fiber as an internal marker. A two-pool mixing model was used to predict diet source utilizing CH4 δ13C. Inclusion of RP did not affect intake or CH4 production (P &gt; 0.05). Methane production per animal averaged 250 g CH4/d and 33 g CH4/kg dry matter intake, across treatments. The CH4 δ13C were −55.5, −60.3, −63.25, −63.35, and −68.7 for 0%RP, 25%RP, 50%RP, 75%RP, and 100%RP, respectively, falling within the reported ranges for C3 or C4 forage diets. Moreover, there was a quadratic effect (P = 0.04) on the CH4 δ13C, becoming more depleted (e.g., more negative) as the diet proportion of RP hay increased, appearing to plateau at 75%RP. Regression between predicted and observed proportions of RP in bahiagrass hay diets based on δ13C from CH4 indicate δ13C to be useful (Adj. R2 = 0.89) for predicting the contribution of RP in C3–C4 binary diets. Data from this study indicate that, while CH4 production may not always be reduced with legume inclusion into C4 hay diets, the δ13C technique is indeed useful for tracking the effect of dietary sources on CH4 emissions.
Leveraging Society Membership for Career Development
Authors: Destounis Stamatia 
Published: June 2023

Abstract
A breast radiologist who is early in their career will be faced with many opportunities that can be both challenging and rewarding. It is helpful to be aware of the resources available in the breast imaging field. Specialty society membership provides opportunities for personal and professional growth. Connections and relationships can be made with other breast radiologists at differing career stages, presenting opportunities to develop mentor-mentee relationships with experienced members and peer-to-peer relationships with colleagues who may have similar professional experiences. The resources available through society membership can assist in career development and help navigate academic and private practice settings.
Gallic acid: a polyphenolic compound potentiates the therapeutic efficacy of cisplatin in human breast cancer cells
Authors: Shruthi S , Mumbrekar Kamalesh D , Rao B S Satish , Shenoy Bhasker K 
Published: June 2023

Abstract
Gallic acid (GA) is a natural polyhydroxyphenolic compound with antioxidant, antimutagenic, anti-inflammatory, and antineoplastic activities. Cisplatin (CPT) is a platinum-based chemotherapeutic drug, and it is the treatment of choice for breast, ovarian, testicular, head, and neck cancers. However, the use of anticancer drugs has undesirable effects on patients due to associated toxicities. Thus, it is necessary to search for alternatives that reduce unintended side effects and enhance anticancer potential. The use of natural compounds with the conventional chemotherapeutic drug is a new aspect of cancer therapy. In the present study, we evaluated the ability of GA in the modulation of anticancer effects of CPT in human breast adenocarcinoma cells (MCF-7) by performing MTT, apoptosis, clonogenic cell survival, and micronucleus assays. GA and CPT showed significant cytotoxic activities in MCF-7 cells in a dose-dependent manner. In combination therapy (GA 2.5, 5.0, and 10 μg/mL + CPT10 μg/mL), GA synergistically reduced the MCF-7 cell viability in contrast to the individual therapies. Cancer cells death by GA is through the induction of apoptosis as observed in the acridine orange and ethidium bromide dual staining method. The frequency of micronuclei (MN) was decreased significantly (P &lt; 0.001) in combinational therapy, possibly reducing the risk of chemotherapy-induced MN. Moreover, GA in mono or combinational therapy did not induce any cytotoxic effects in normal breast epithelial cells (MCF-10A). GA did not show any significant difference in colony inhibition compared to CPT. This outcome shows its differential effects in normal and cancerous cells. Hence, the combination GA with chemotherapeutic drugs could represent a promising alternative therapy in cancer treatment with minimal side effects.
Sortilin acts as an endocytic receptor for α‐synuclein fibril
Authors: Ishiyama Shun , Hasegawa Takafumi , Sugeno Naoto , Kobayashi Junpei , Yoshida Shun , Miki Yasuo , Wakabayashi Koichi , Fukuda Mitsunori , Kawata Yasushi , Nakamura Takaaki , Sato Kazuki , Ezura Michinori , Kikuchi Akio , Takeda Atsushi , Aoki Masashi 
Published: June 2023

AbstractCell‐to‐cell spreading of misfolded α‐synuclein (αSYN) is supposed to play a key role in the pathological progression of Parkinson's disease (PD) and other synucleinopathies. Receptor‐mediated endocytosis has been shown to contributes to the uptake of αSYN in both neuronal and glial cells. To determine the receptor involved in αSYN endocytosis on the cell surface, we performed unbiased, and comprehensive screening using a membrane protein library of the mouse whole brain combined with affinity chromatography and mass spectrometry. The candidate molecules hit in the initial screening were validated by co‐immunoprecipitation using cultured cells; sortilin, a vacuolar protein sorting 10 protein family sorting receptor, exhibited the strongest binding to αSYN fibrils. Notably, the intracellular uptake of fibrillar αSYN was slightly but significantly altered, depending on the expression level of sortilin on the cell surface, and time‐lapse image analyses revealed the concomitant internalization and endosomal sorting of αSYN fibrils and sortilin. Domain deletion in the extracellular portion of sortilin revealed that the ten conserved cysteines (10CC) segment of sortilin was involved in the binding and endocytosis of fibrillar αSYN; importantly, pretreatment with a 10CC domain‐specific antibody significantly hindered αSYN fibril uptake. The presence of sortilin in the core structure of Lewy bodies and glial cytoplasmic inclusions in the brain of synucleinopathy patients was confirmed via immunohistochemistry, and the expression level of sortilin in mesencephalic dopaminergic neurons may be altered with disease progression. These results provide compelling evidence that sortilin acts as an endocytic receptor for pathogenic form of αSYN, and yields important insight for the development of disease‐modifying targets for synucleinopathies.
Innovative Projects: A Unique Approach to Telehealth Education
Authors: Roberto Anka , O’Rourke Jenny , Khairat Saif , Gustin Tina , Rutledge Carolyn 
Published: June 2023

Abstract
During the COVID-19 pandemic, telehealth utilization grew astronomically, encouraging more institutions of higher education to become innovative and proactive in preparing health care providers to deliver high-quality telehealth care. Telehealth can be creatively implemented throughout health care curricula given the appropriate guidance and tools. This article speaks to the development of student telehealth projects as part of the work of a national taskforce funded by the Health Resources and Services Administration and charged with the development of a telehealth toolkit. Proposed telehealth projects allow students to take the lead in their innovative learning and allow faculty to facilitate project-based evidence-based pedagogy.
Surgeon Experience Influences Robotics Learning Curve for Minimally Invasive Lumbar Fusion
Authors: Shahi Pratyush , Subramanian Tejas , Maayan Omri , Korsun Maximilian , Singh Sumedha , Araghi Kasra , Singh Nishtha , Asada Tomoyuki , Tuma Olivia , Vaishnav Avani , Sheha Evan , Dowdell James , Qureshi Sheeraz , Iyer Sravisht 
Published: June 2023

Study Design.Retrospective review of prospectively collected data.Objective.To analyze the learning curves of three spine surgeons for robotic minimally invasive transforaminal lumbar interbody fusion (MI-TLIF).Summary of Background Data.Although the learning curve for robotic MI-TLIF has been described, the current evidence is of low quality with most studies being single-surgeon series.Materials and Methods.Patients who underwent single-level MI-TLIF with three spine surgeons (years in practice: surgeon 1: 4, surgeon 2: 16, and surgeon 3: two) using a floor-mounted robot were included. Outcome measures were operative time, fluoroscopy time, intraoperative complications, screw revision, and patient-reported outcome measures. Each surgeon’s cases were divided into successive groups of 10 patients and compared for differences. Linear regression and cumulative sum (CuSum) analyses were performed to analyze the trend and learning curve, respectively.Results.A total of 187 patients were included (surgeon 1: 45, surgeon 2: 122, and surgeon 3: 20). For surgeon 1, CuSum analysis showed a learning curve of 21 cases with the attainment of mastery at case 31. Linear regression plots showed negative slopes for operative and fluoroscopy time. Both learning phase and postlearning phase groups showed significant improvement in patient-reported outcome measures. For surgeon 2, CuSum analysis demonstrated no discernible learning curve. There was no significant difference between successive patient groups in either operative time or fluoroscopy time. For surgeon 3, CuSum analysis demonstrated no discernible learning curve. Even though the difference between successive patient groups was not significant, cases 11 to 20 had an average operative time of 26 minutes less than cases 1–10), suggesting an ongoing learning curve.Conclusions.Surgeons who are well-experienced can be expected to have no or minimal learning curve for robotic MI-TLIF. Early attendings are likely to have a learning curve of around 21 cases with the attainment of mastery at case 31. Learning curve does not seem to impact clinical outcomes after surgery.Level of Evidence.Level 3.
International Analgesia and Sedation Weaning and Withdrawal Practices in Critically Ill Adults: The Adult Iatrogenic Withdrawal Study in the ICU*
Authors: Bolesta Scott , Burry Lisa , Perreault Marc M. , Gélinas Céline , Smith Kathryn E. , Eadie Rebekah , Carini Federico C. , Saltarelli Katrianna , Mitchell Jennifer , Harpel Jamie , Stewart Ryan , Riker Richard R. , Fraser Gilles L. , Erstad Brian L. ,   on behalf of the AduLt iatrogEnic withdRawal sTudy in the ICU (ALERT-ICU) Study Investigators
Published: June 2023

OBJECTIVES:
Iatrogenic withdrawal syndrome (IWS) associated with opioid and sedative use for medical purposes has a reported high prevalence and associated morbidity. This study aimed to determine the prevalence, utilization, and characteristics of opioid and sedative weaning and IWS policies/protocols in the adult ICU population.

DESIGN:
International, multicenter, observational, point prevalence study.

SETTING:
Adult ICUs.

PATIENTS:
All patients aged 18 years and older in the ICU on the date of data collection who received parenteral opioids or sedatives in the previous 24 hours.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
ICUs selected 1 day for data collection between June 1 and September 30, 2021. Patient demographic data, opioid and sedative medication use, and weaning and IWS assessment data were collected for the previous 24 hours. The primary outcome was the proportion of patients weaned from opioids and sedatives using an institutional policy/protocol on the data collection day. There were 2,402 patients in 229 ICUs from 11 countries screened for opioid and sedative use; 1,506 (63%) patients received parenteral opioids, and/or sedatives in the previous 24 hours. There were 90 (39%) ICUs with a weaning policy/protocol which was used in 176 (12%) patients, and 23 (10%) ICUs with an IWS policy/protocol which was used in 9 (0.6%) patients. The weaning policy/protocol for 47 (52%) ICUs did not define when to initiate weaning, and the policy/protocol for 24 (27%) ICUs did not specify the degree of weaning. A weaning policy/protocol was used in 34% (176/521) and IWS policy/protocol in 9% (9/97) of patients admitted to an ICU with such a policy/protocol. Among 485 patients eligible for weaning policy/protocol utilization based on duration of opioid/sedative use initiation criterion within individual ICU policies/protocols 176 (36%) had it used, and among 54 patients on opioids and/or sedatives ≥ 72 hours, 9 (17%) had an IWS policy/protocol used by the data collection day.

CONCLUSIONS:
This international observational study found that a small proportion of ICUs use policies/protocols for opioid and sedative weaning or IWS, and even when these policies/protocols are in place, they are implemented in a small percentage of patients.
Orthokeratology for Slowing Myopia Progression in Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Tang Kai , Si Junkang , Wang Xingrong , Lu Xiuzhen , Bi Hongsheng 
Published: June 2023

Objective:
To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) on the effects of orthokeratology for slowing myopia progression in children.

Methods:
We performed a specific search on PubMed, Embase, Cochrane Library, Clinical Trials, CNKI, SinoMed, and Wanfang Data for RCTs conducted up to October 1, 2022. We pooled the weighted mean difference (WMD) between the orthokeratology and control groups for axial length (AL) elongation and the odds ratio (OR) for rates of adverse events and dropout.

Results:
Seven RCTs involving 655 eyes were included. There were significant differences in the effects of orthokeratology versus control in slowing AL elongation with WMD of −0.11 mm (95% confidence interval (CI), −0.13 to −0.08; P<0.01) at 6 months, −0.16 mm (95% CI, −0.18 to −0.13; P<0.01) at 12 months, −0.23 mm (95% CI, −0.29 to −0.18; P<0.01) at 18 months, and −0.28 mm (95% CI, −0.38 to −0.19; P<0.01) at 24 months, respectively. Myopia control rate declined, with 64%, 53%, 50%, and 47% recorded for 6, 12, 18, and 24 months, respectively. There was no statistical significance for adverse events between orthokeratology and control groups (OR=2.63, 95% CI, 0.72–9.61; P=0.11).

Conclusion:
Orthokeratology can effectively slow myopia progression in children, and the efficacy of myopia control decreases with time.
Blood–Brain Barrier Dysfunction and Exposure to Head Impacts in University Football Players
Authors: Jones Casey M. A. , Kamintsky Lyna , Parker Ellen , Kureshi Nelofar , Audas Lorelei , Wilson Lisa , Champagne Allen A. , Boulanger Marie-Michelle , DiStefano Vincent , Fenerty Lynne , Bowen Chris , Beyea Steven , Atkinson Christina , Clarke David B. , Friedman Alon 
Published: June 2023

Objective:
To investigate the link between dysfunction of the blood–brain barrier (BBB) and exposure to head impacts in concussed football athletes.

Design:
This was a prospective, observational pilot study.

Setting:
Canadian university football.

Participants:
The study population consisted of 60 university football players, aged 18 to 25. Athletes who sustained a clinically diagnosed concussion over the course of a single football season were invited to undergo an assessment of BBB leakage.

Independent variables:
Head impacts detected using impact-sensing helmets were the measured variables.

Main outcome measures:
Clinical diagnosis of concussion and BBB leakage assessed using dynamic contrast-enhanced MRI (DCE-MRI) within 1 week of concussion were the outcome measures.

Results:
Eight athletes were diagnosed with a concussion throughout the season. These athletes sustained a significantly higher number of head impacts than nonconcussed athletes. Athletes playing in the defensive back position were significantly more likely to sustain a concussion than remain concussion free. Five of the concussed athletes underwent an assessment of BBB leakage. Logistic regression analysis indicated that region-specific BBB leakage in these 5 athletes was best predicted by impacts sustained in all games and practices leading up to the concussion—as opposed to the last preconcussion impact or the impacts sustained during the game when concussion occurred.

Conclusions:
These preliminary findings raise the potential for the hypothesis that repeated exposure to head impacts may contribute to the development of BBB pathology. Further research is needed to validate this hypothesis and to test whether BBB pathology plays a role in the sequela of repeated head trauma.
Modern approaches to treating Zenker's diverticulum
Authors: Fair Lucas , Ward Marc A. 
Published: June 2023

Purpose of review
Zenker's diverticulum is the most common hypopharyngeal diverticulum. Patients with Zenker's diverticulum may require surgical treatment, which can be performed via an open surgical or endoscopic approach. A new endoscopic technique that is now being used for Zenker's diverticulum is Zenker Per Oral Endoscopic Myotomy (ZPOEM). ZPOEM has demonstrated promising results, and may have certain advantages over the other endoscopic treatments. The purpose of this review article is to evaluate the various surgical and endoscopic treatment options for Zenker's diverticulum, while specifically focusing on ZPOEM.

Recent findings
Endoscopic approaches have become the first-line therapy for Zenker's diverticulum, replacing the traditional open approach, because of the less invasive nature of the endoscopic procedures, improved rates of morbidity, and quicker recovery times. Recent studies evaluating ZPOEM have demonstrated that it is technically feasible and highly efficacious. In addition, it has a low rate of clinical recurrence and adverse events. When compared with other endoscopic techniques for treating Zenker's diverticulum, ZPOEM appears to have improved outcomes.

Summary
ZPOEM has been recently implemented in the algorithm of Zenker's diverticulum management. Further comparative and prospective studies focusing on long-term follow-up are still needed; however, ZPOEM appears to be an excellent option for patients suffering from Zenker's diverticulum.