bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elements of End-of-Life Discussions Associated With Patients’ Reported Outcomes and Actual End-of-Life Care in Patients With Pretreated Lung Cancer
Authors: Hasegawa Takaaki , Okuyama Toru , Uemura Takehiro , Matsuda Yoshinobu , Otani Hiroyuki , Shimizu Junichi , Horio Yoshitsugu , Watanabe Naohiro , Yamaguchi Teppei , Fukuda Satoshi , Oguri Tetsuya , Maeno Ken , Taniguchi Yoshihiko , Nosaki Kaname , Fukumitsu Kensuke , Akechi Tatsuo 
Published: September 2023

Abstract

Background
End-of-life discussions for patients with advanced cancer are internationally recommended to ensure consistency of end-of-life care with patients’ values. This study examined the elements of end-of-life discussions associated with end-of-life care.

Materials and Methods
We performed a prospective observational study among consecutive patients with pretreated non-small cell lung cancer after the failure of first-line chemotherapy. We asked oncologists whether they had ever discussed “prognosis,” “do not attempt resuscitation,” “hospice,” and “preferred place of death” with a patient at baseline. The quality of life (QOL) and depressive symptoms of patients were assessed using validated questionnaires at baseline and 3 months later. The end-of-life care that patients received was investigated using medical records. Oncologists’ compassion and caregivers’ preferences for hospice care were also assessed using questionnaires. Multiple regression analyses were conducted to examine the association between elements of end-of-life discussions and patient-reported outcomes as well as actual end-of-life care.

Results
We obtained 200 valid responses at baseline, 147 valid responses 3 months later, and 145 data points for medical care at the end-of-life stage. No element of the end-of-life discussion between the patient and their oncologist was significantly associated with patients’ reported outcomes or actual end-of-life care. In addition, oncologists’ compassion was significantly associated with improvement in both comprehensive QOL and depressive symptoms, and caregivers’ preferences for hospice care and high educational level were significantly associated with hospice death.

Conclusion
Oncologist-patient alliances and caregivers’ involvement in end-of-life discussions may be influential in achieving optimal end-of-life care.
Microtubule-associated protein SlMAP70 interacts with IQ67-domain protein SlIQD21a to regulate fruit shape in tomato
Authors: Bao Zhiru , Guo Ye , Deng Yaling , Zang Jingze , Zhang Junhong , Deng Yingtian , Ouyang Bo , Qu Xiaolu , Bürstenbinder Katharina , Wang Pengwei 
Published: September 2023

Abstract
Tomato (Solanum lycopersicum) fruit shape is related to microtubule organization and the activity of microtubule-associated proteins (MAPs). However, insights into the mechanism of fruit shape formation from a cell biology perspective remain limited. Analysis of the tissue expression profiles of different microtubule regulators revealed that functionally distinct classes of MAPs, including members of the plant-specific MICROTUBULE-ASSOCIATED PROTEIN 70 (MAP70) and IQ67 DOMAIN (IQD, also named SUN in tomato) families, are differentially expressed during fruit development. SlMAP70-1–3 and SlIQD21a are highly expressed during fruit initiation, which relates to the dramatic microtubule pattern rearrangements throughout this developmental stage of tomato fruits. Transgenic tomato lines overexpressing SlMAP70-1 or SlIQD21a produced elongated fruits with reduced cell circularity and microtubule anisotropy, while their loss-of-function mutants showed the opposite phenotype, harboring flatter fruits. Fruits were further elongated in plants coexpressing both SlMAP70-1 and SlIQD21a. We demonstrated that SlMAP70s and SlIQD21a physically interact and that the elongated fruit phenotype is likely due to microtubule stabilization induced by the SlMAP70–SlIQD21a interaction. Together, our results identify SlMAP70 proteins and SlIQD21a as important regulators of fruit elongation and demonstrate that manipulating microtubule function during early fruit development provides an effective approach to alter fruit shape.
Endoscopic retrograde cholangiopancreatography as a single-modality ‘gold-standard’ treatment for common bile duct stones in the elderly
Authors: Manson David , Soliman Faris , Mohamed Usama , Somasekar Krishnamurthy 
Published: September 2023

Abstract

Background
There are more octogenarians presenting with gallstone disease each year. Many are not suitable for surgical intervention. An alternative treatment option for common bile duct stones in the elderly is endoscopic retrograde cholangiopancreatography (ERCP) with or without stent insertion.

Methods
We conducted a retrospective study using a prospectively collected database, analysing the outcomes of consecutive patients &gt;80 years old who underwent an ERCP in a single centre for the treatment of common bile duct stones.

Results
In total, 156 patients, with a median age of 91 years, underwent an ERCP for choledocholithiasis over a 3-year period. ERCP was successful in 90% of patients but a proportion required repeat intervention. Forty-six (29%) patients had a concurrently inserted stent due to incomplete stone extraction. Six (4%) patients required a post-ERCP cholecystectomy due to ongoing symptoms. The overall ERCP complication rate was 7% (4% Clavien-Dindo 1 and 3% Clavien-Dindo 2), with no cases of post-ERCP pancreatitis or death. Patients were followed up over 5 years following index ERCP. There was a 60% 3-year survival and 30% 5-year survival rate following index ERCP. Importantly, of those who did not survive, only four patients (2.6%) had a death attributable to a biliary cause and none were fit for definitive surgery.

Conclusions
ERCP can be considered as a possible definitive management option for treating common bile duct stones in the elderly, particularly in the comorbid population. Concurrent stenting is an effective temporizing strategy and mitigator of biliary-related readmission, but routine stent changes should be considered.
Key messages What is already known on this topic Current guidelines advocate for laparoscopic cholecystectomy and common bile duct exploration in patients with choledocholithiasis. What this study adds Endoscopic retrograde cholangiopancreatography with or without stent insertion is a safe, alternative single-treatment modality for choledocholithiasis in the elderly comorbid population. How this study might affect research, practice, or policy Studies and guidelines evaluating treatment options for choledocholithiasis may be altered to accommodate patient-specific factors, including age and comorbid status, and the concurrent use of stenting as a either a temporizing or longer-term measure for complex stone disease.
Two Conceptions of Instrumental Thought
Authors: O’Connell Rory 
Published: September 2023

Abstract
According to a dominant assumption the truth of instrumental thoughts—thoughts in which one action is identified as a means to another—are not affected by agents’ normative conceptions of their ends. Agents could in principle grasp these thoughts, and thereby the correct means to their ends, without consulting any conception they may have as to the pursuit-worthiness of those ends. I argue this assumption (the ‘Theoretical Conception’) prevents us from explaining how agents can identify means to their ends. I sketch an alternative account according to which the contents of instrumental thoughts are directly determined by agent's reasons for acting. This is explained by the fact that an agent's reasons for action reveal what they take the good of their ends to be. Ultimately, I argue, agents must have a conception of their final ends as intrinsically good if they are to successfully specify means to them.
Why Must Incompatibility Be Symmetric?
Authors: Simonelli Ryan 
Published: September 2023

Abstract
Why must incompatibility be symmetric? An odd question, but recent work in the semantics of non-classical logic, which appeals to the notion of incompatibility as a primitive and defines negation in terms of it, has brought this question to the fore. Francesco Berto proposes such a semantics for negation argues that, since incompatibility must be symmetric, double negation introduction must be a law of negation. However, he offers no argument for the claim that incompatibility really must be symmetric. Here, I provide such an argument, showing that, insofar as we think of incompatibility in normative pragmatic terms, it can play its basic pragmatic function only if it is symmetric. The upshot is that we can vindicate Berto’s claim about the symmetry of incompatibility but only if we, pace Berto, think about incompatibility, in the first instance, as a pragmatic relation between acts rather than a semantic relation between contents.
Vagus Nerve Stimulation Paired With Mobility Training in Chronic Ischemic Stroke: A Case Report
Authors: Kimberley Teresa J , Prudente Cecília N , Engineer Navzer D , Dickie David Alexander , Bisson Teresa A , Van de Winckel Ann 
Published: September 2023

Abstract

Objective
The purpose of this case report is to describe pairing vagus nerve stimulation (VNS) with mobility training in an individual after stroke.

Methods
A 53-year-old man with left hemiparesis 14.2 months after an ischemic stroke participated in a pilot study investigating the safety and feasibility of VNS paired with upper limb rehabilitation. In addition to upper limb impairment, the participant had impaired gait and wanted to improve his mobility. A single-subject design investigation of VNS paired with self-directed mobility training was conducted. Following the conclusion of the pilot study, the participant was instructed to complete daily sessions of self-activated VNS paired with walking or stationary biking. The 10-Meter Walk Test and timed distance (6-Minute Walk Test) were assessed at 4 baseline points and at 3 to 41 months after mobility training.

Results
The participant had stable baseline values and was classified as a household ambulator with a quad cane. After VNS-paired mobility training, statistically significant improvements were observed in all measures, with the greatest improvements at 9 months exceeding the minimal detectable change: self-selected gait speed from 0.34 (standard deviation [SD] = 0.01) to 0.60 meters/second, fast gait speed from 0.37 (SD = 0.03) to 0.79 meters/second, and 6-Minute Walk Test distance from 106.91 (SD = 6.38) to 179.83 meters. The participant reported increased confidence and balance when walking. No falls or adverse events were reported.

Conclusion
The participant demonstrated improved gait speed and timed distance after VNS-paired mobility training. Randomized, blinded trials are needed to determine treatment efficacy.

Impact
This is the first documented case of VNS-paired mobility training in an individual with chronic poststroke gait impairments. VNS paired with mobility training may improve poststroke gait impairments.
Treating acute migraine with ubrogepant
Authors: Schoenfuss Erin S. 
Published: September 2023

ABSTRACT
Acute migraine affects millions of people and is one of the most common primary care complaints in the United States. Available first-line abortive treatments are limited and vary in efficacy. Newer medications such as calcitonin gene-related peptide (CGRP) receptor antagonists may be a useful alternative. This article describes the use of ubrogepant, a new CGRP receptor antagonist, in a patient with contraindications to traditional medications used for acute migraine.
How to avoid pitfalls when referring patients to otolaryngology
Authors: Dey Dennis 
Published: September 2023

ABSTRACT
Delayed, faulty, incomplete, or misdiagnosed referrals to otolaryngology (also called ear, nose, and throat, or ENT) can result in physical and monetary harm to the patient and time spent by clinicians in reordering the appropriate diagnostic tests. This article describes how to refer patients to ENT in the most time- and cost-effective ways, and addresses initial management in primary care.
CBD oil
Authors: Felker Lori 
Published: September 2023

ABSTRACT
Cannabinoid (CBD) oil is a trend in self-care management. In this digital age, patients have access to products from across the globe, and these products may not be regulated. Healthcare providers must be at the forefront of the latest trends in medicine and alternative therapies to better serve patients' needs. This article reviews various medical conditions for which CBD oil already is being used, its other medicinal uses, major adverse reactions, and what patients should know before they decide to consume CBD oil.
Maximizing patient safety when prescribing opioids for pain management
Authors: Judy Megan , Sams David , Poulton Stephon 
Published: September 2023

ABSTRACT
Cytochrome P450 enzyme metabolism is altered by environmental and genetic factors, which can affect the efficacy and safety of opioids. This article describes CYP polymorphisms and how pharmacogenetic testing could be used to help clinicians make safer decisions about opioid use in patients.
Heterozygous and homozygous gene knockout of the 5-HT1B receptor have different effects on methamphetamine-induced behavioral sensitization
Authors: Moriya Yuki , Kasahara Yoshiyuki , Ishihara Kana , Hall Frank Scott , Hagino Yoko , Hen René , Ikeda Kazutaka , Uhl George R. , Sora Ichiro 
Published: September 2023

The psychostimulant drug methamphetamine (METH) causes euphoria in humans and locomotor hyperactivity in rodents by acting on the mesolimbic dopamine (DA) pathway and has severe abuse and addiction liability. Behavioral sensitization, an increased behavioral response to a drug with repeated administration, can persist for many months after the last administration. Research has shown that the serotonin 1B (5-HT1B) receptor plays a critical role in the development and maintenance of drug addiction, as well as other addictive behaviors. This study examined the role of 5-HT1B receptors in METH-induced locomotor sensitization using 5-HT1B knockout (KO) mice. To clarify the action of METH in 5-HT1B KO mice the effects of METH on extracellular levels of DA (DAec) and 5-HT (5-HTec) in the caudate putamen (CPu) and the nucleus accumbens (NAc) were examined. Locomotor sensitization and extracellular monoamine levels were determined in wild-type mice (5-HT1B +/+), heterozygous 5-HT1B receptor KO (5-HT1B +/−) mice and homozygous 5-HT1B receptor KO mice (5-HT1B −/−).
Behavioral sensitization to METH was enhanced in 5-HT1B −/− mice compared to 5-HT1B +/+ mice but was attenuated in 5-HT1B +/− mice compared to 5-HT1B +/+ and 5-HT1B −/− mice. In vivo, microdialysis demonstrated that acute administration of METH increases DAec levels in the CPu and NAc of 5-HT1B KO mice compared to saline groups. In 5-HT1B +/− mice, METH increased 5-HTec levels in the CPu, and DAec levels in the NAc were higher than in others.5-HT1B receptors play an important role in regulating METH-induced behavioral sensitization.
Preoperative optimization and rapid discharge after coronary artery bypass grafting
Authors: Ponnambalam Menaka , Alex Rozen M. 
Published: September 2023

Purpose of review
This review discusses current guidelines and evidence-based care for the preoperative optimization of patients who are undergoing coronary artery bypass grafting (CABG) and for enabling rapid discharge after surgery.

Recent findings
Since the Enhanced Recovery After Cardiac Surgery Society (ERAS Cardiac) issued guidelines for perioperative care, in 2019, there has been a significant body of research that has added to and provided further guidance regarding preoperative optimization and accelerated recovery after CABG.

Summary
A review of the current literature provides a framework for a pragmatic approach to preoperative optimization, utilizing the time from referral to surgery to mitigate multiple aspects of the patient condition, leading to improved patient outcomes and reduced length of stay and cost to the healthcare system.
Social and Health Care Utilization Factors Associated With Ophthalmic Visit Nonadherence in Glaucoma: An All of Us Study
Authors: Wu Jo-Hsuan , Varkhedi Varsha , Radha Saseendrakumar Bharanidharan , Acuff Kaela , Weinreb Robert N. , Baxter Sally L. 
Published: September 2023

Précis:
In a diverse nationwide cohort, lower education and income levels, cost saving on medications, fewer past-year medical/specialist visits, and concerns regarding dissimilarity with health care providers were risk factors for ophthalmic visit nonadherence among glaucoma patients.

Purpose:
The purpose of this study was to characterize social and health care utilization factors associated with nonadherence with ophthalmic visits among patients with glaucoma.

Materials and Methods:
Glaucoma patients in the All of Us database who completed the Healthcare Access and Utilization Survey were included and categorized into “visit” and “nonvisit” groups based on visit adherence, defined by self-reported past-year encounters with eyecare providers (yes/no). Data regarding potential factors affecting ophthalmic visit adherence, including past-year medical visits, inabilities to afford health care, and self-reported reasons for delayed care, were extracted. χ2 tests and logistic regression were used to compare the 2 groups. Odds ratios (ORs) of visit adherence were analyzed for potential risk factors.

Results:
Of 5739 glaucoma patients, 861 (15%) were in the nonvisit group. More participants in the visit group reported past-year general doctor/specialist visits (94%/65%; vs. nonvisit group: 89%/49.3%; P<0.05). The nonvisit group reported greater difficulty in affording medical care and learning about medical conditions, and higher rates of delayed/missed health care access for various concerns (P<0.05). Older age (OR=1.02, 1.01–1.03), higher education (OR=1.25, 1.13–1.40), and income level (OR=1.06, 1.01–1.11), not employed for wages (OR=1.28, 1.08–1.53), and higher health care utilization in general medical/specialist visits (ORs range:1.08–1.90) were associated with visit adherence (P<0.05). Visit nonadherence was associated with cost saving on medication (OR=0.62, 0.40–0.97) and delaying/avoiding seeing health care providers because of dissimilarity (OR=0.84, 0.71–0.99) (P<0.05).

Conclusions:
This study builds on prior literature by identifying potentially modifiable factors associated with visit nonadherence and underutilization of eyecare in glaucoma. These may inform strategies to improve real-world ophthalmic visit adherence and identify patients who might benefit from additional support.
Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine KCONVAC in Chinese Children: Randomized, Double-blind, Placebo-controlled Phase 1 and 2 Trials
Authors: Liu Jiankai , Huang Baoying , Li Guifan , Huang Tao , Wang Danni , Zhang Li , Deng Yao , Chang Xianyun , Liu Yafei , Li Weiqi , Zhang Siyuan , Huang Weijin , Tan WenJie , Gao Lidong 
Published: September 2023

Background:
It is important to extend the indication of severe acute respiratory syndrome coronavirus 2 vaccine to children to improve the vaccine intake rate and reduce infection in this population.

Methods:
In 2 phase 1 and phase 2 randomized, double-blind and placebo-controlled trials, 84 and 480 Chinese healthy children 3 to 17 years old were enrolled, respectively, and randomized in 3:1 ratio to receive 2 doses of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine, KCONVAC or placebo. The 2 doses were given 28 days apart. Adverse events (AEs) were recorded through Day 28 after each dosing. Live virus neutralizing antibody and receptor binding domain antibody (RBD-IgG) were tested before vaccination and after the second dose.

Results:
Two doses of the vaccine, KCONVAC, elicited geometric mean titers of 142–150 for neutralizing antibody and 4154–4253 for RBD-IgG 28 days after the second dose. Seroconversion rates were 100% after 2 doses for both antibodies in both trials. The predominant AEs were injection-site pain, cough and fever. Most AEs were grade 1 or 2 in intensity. Five participants reported 6 vaccination-unrelated serious AEs in the phase 2 trial.

Conclusions:
Two doses of this study vaccine, KCONVAC, were well tolerated and immunogenic in children 3 to 17 years of age.
Prevalence and Prognostic Significance of PIK3CA Mutation and CNV Status and Phosphorylated AKT Expression in Patients With Cervical Cancer Treated With Primary Surgery
Authors: Martell Kevin , McIntyre John B. , Abedin Tasnima , Kornaga Elizabeth N. , Chan Angela M.Y. , Enwere Emeka , Köbel Martin , Dean Michelle L. , Phan Tien , Ghatage Prafull , Lees-Miller Susan P. , Doll Corinne M. 
Published: September 2023

Currently, there are limited and conflicting reports on the prognostic utility of PIK3CA and associated pathway markers for cervical cancers treated with primary surgical management. Moreover, current studies are lacking complete characterization of adjuvant treatment with RT and/or chemotherapy. We aimed to document the prevalence, clinicopathologic, adjuvant treatment details, and prognostic value of PI3K/AKT pathway mutations and copy number variation and phosphorylated AKT status in patients with cervical cancers treated with primary surgery. A clinicopathologic review was performed on a retrospective cohort of 185 patients with cervical cancer, treated with primary surgery at a single tertiary institution. Next-generation sequencing and digital PCR was used to determine PI3K/AKT pathway mutational status and PIK3CA copy number variation, respectively, and fluorescent immunohistochemistry measured phosphorylated AKT expression. In all, 179 of 185 (96.8%) of tumors were successfully sequenced; 48 (26.8%) were positive for PI3K/AKT pathway mutations—the majority (n=37, 77.1%) PIK3CA mutations. PIK3CA mutation was associated with pathologically positive lymph nodes [12 (32%) vs. 22 (16%); P=0.022] and indication for postoperative chemoradiotherapy [17 (45.9%) vs. 32 (22.5%); P=0.004]. On multivariable analysis, PIK3CA status was not associated with overall survival (P=0.103) or progression-free survival (P=0.240) at 5 yrs, nor was PIK3CA copy number variation status. phosphorylated AKT ≤ median significantly predicted for progression-free survival [multivariable hazard ratio 0.39 (0.17–0.89; P=0.025)] but not overall survival (P=0.087). The correlation of PIK3CA with pathologic positive lymph node status yet lack of association with survival outcomes may be due to the use of adjuvant postoperative therapy. PIK3CA assessment before radical hysterectomy may help identify patients with a higher risk of node-positive disease.