bluuebunny/crossref_metadata_2025_split huggingface dataset:
Common Disorders of the Larynx
Authors: Jahn Anthony F , Cho Youngnan Jenny 
Published: September 2024

Abstract
A handful of laryngeal disorders account for the majority of vocal complaints in singers. These are mostly benign and respond well to treatment. This chapter presents a description of these disorders, with illustrations, and an overview of the causes, symptoms, and management. The purpose is to familiarize singers with these problems and to reduce the anxiety provoked by diagnoses such as “vocal nodules” and “vocal fold hemorrhage.”
The Singer
Authors: Jahn Anthony F , Cho Youngnan Jenny 
Published: September 2024

Abstract
This chapter steps back a bit, to consider singing as an art form. The authors propose that singing is unique among all the arts, melding left brain and right brain input, and requiring the performer to be both artist and artisan. It is an appreciation of the skill, beauty, and unparalleled nature of vocal performance, and pays tribute to singers and the singing voice.
A Systematic Approach to Evaluating Instrumental Variable Assumptions: Applied Example of Glucose-lowering Medications and Risk for Hospitalized Heart Failure in Older Adults
Authors: Htoo Phyo T , Edwards Jessie K , Gokhale Mugdha , Pate Virginia , Buse John B , Jonsson-Funk Michele , Stürmer Til 
Published: September 2024

Abstract
One obstacle to adopting instrumental variable (IV) methods in pharmacoepidemiology is their reliance on strong, unverifiable assumptions. We can falsify IV assumptions by leveraging the causal structure, which can strengthen or refute their plausibility and increase the validity of effect estimates. We illustrate a systematic approach to evaluate calendar time IV assumptions in estimating the known effect of thiazolidinediones on hospitalized heart failure. Using cohort entry time before and after 09/2010, when the U.S. Food and Drug Administration issued a safety communication as a proposed IV, we estimated IV and propensity score-weighted 2-year risk differences (RDs) using Medicare data (2008-2014). We (i) performed inequality tests, (ii) identified the negative control IV/outcome using causal assumptions, (iii) estimated RDs after narrowing the calendar time range and excluding patients likely associated with unmeasured confounding, (iv) derived bounds for RDs, and (v) estimated the proportion of compliers and their characteristics. The findings revealed that IV assumptions were violated and RDs were extreme, but the assumptions became more plausible upon narrowing the calendar time range and restricting the cohort by excluding prevalent heart failure (the strongest measured predictor of outcome). Systematically evaluating IV assumptions could help detect bias in IV estimators and increase their validity.
The impact of media-based mental health campaigns on male help-seeking: a systematic review
Authors: Duthie Grant , Reavley Nicola , Wright Judith , Morgan Amy 
Published: September 2024

Abstract
More than half of all men do not seek professional help for depression, suicide and anxiety. Although media-based campaigns represent a promising health promotion intervention to improve male help-seeking, it is unclear what communication strategies in extant mental health media-based campaigns are effective for men. The aim of this systematic review was to synthesize information about the effectiveness of these campaigns on male help-seeking outcomes. A search was conducted of electronic databases and gray literature. Studies were eligible if they examined the effectiveness of a media-based campaign targeting male help-seeking attitudes, beliefs, intentions or behaviors in relation to mental disorders, distress, suicide or self-harm. Twenty-two studies of varying quality met the eligibility criteria. Most studies targeting mental health or depression were found to positively influence male help-seeking. There were mixed results for suicide prevention campaigns. Some evidence suggests that overall, brochure-based campaigns impact help-seeking. The use of male or mixed-gender campaign imagery produced similar results. The choice of message framing appeared to influence help-seeking outcomes. Despite substantial heterogeneity in campaign approaches and difficulties isolating the effects of campaign delivery from messaging, the review indicates that media-based campaigns can play a role in improving male help-seeking for mental health difficulties. Mounting evidence suggests that messaging and delivery should align with male communication preferences. However, high-quality, targeted research is required to evaluate the circumstances in which various campaign delivery and messaging components are effective in improving male help-seeking for poor mental health and suicidality.
Inflorescence development in female cannabis plants is mediated by photoperiod and gibberellin
Authors: Alter Hanan , Sade Yael , Sood Archit , Carmeli-Weissberg Mira , Shaya Felix , Kamenetsky-Goldstein Rina , Bernstein Nirit , Spitzer-Rimon Ben 
Published: September 2024

Abstract
In cannabis seedlings, the initiation of solitary flowers is photoperiod-independent. However, when cannabis reaches the adult stage, short-day photoperiod (SD) triggers branching of the shoot apex and a reduction in internode length, leading to development of a condensed inflorescence. We demonstrate that SD affects cannabis plants in two distinct phases: the first includes rapid elongation of the internodes and main stem, and occurring from Day 5 to Day 10 of plant cultivation under SD; in the second phase, elongation of newly developed internodes ceases, and a condensed inflorescence is formed. Exposure of plants to alternating photoperiods revealed that inflorescence onset requires at least three consecutive days of SD, and SD is consistently required throughout inflorescence maturation to support its typical condensed architecture. This photoperiod-dependent morphogenesis was associated with a decrease in gibberellin (GA4) and auxin levels in the shoot apex. Reverting the plants to a long-day photoperiod (LD) increased GA4 and auxin levels, leading to inflorescence disassembly, internode elongation, and subsequent resumption of LD growth patterns. Similar developmental patterns were observed under SD following the application of exogenous GA (and not auxin), which also impeded inflorescence development. Nevertheless, additional studies will help to further evaluate auxin’s role in these developmental changes. We propose a crucial role for GA in sexual reproduction and inflorescence development in female cannabis by mediating photoperiod signaling in the inflorescence tissues.
Impact of adequate empirical combination therapy on mortality in septic shock due to Pseudomonas aeruginosa bloodstream infections: a multicentre retrospective cohort study
Authors: Vena Antonio , Schenone Michela , Corcione Silvia , Giannella Maddalena , Pascale Renato , Giacobbe Daniele Roberto , Muccio Marco , Mornese Pinna Simone , Pari Bianca , Giovannenze Francesca , Geremia Nicholas , Mikulska Malgorzata , Taddei Eleonora , Sangiorgi Flavio , Bavaro Davide Fiore , Scaglione Vincenzo , Vassia Veronica , Merli Marco , Bartoletti Michele , Viale Pierluigi , De Rosa Francesco Giuseppe , Bassetti Matteo 
Published: September 2024

Abstract

Objectives
To determine the association of adequate empirical combination therapy (AECT) with 30-day all-cause mortality in patients with septic shock due to Pseudomonas aeruginosa bloodstream infections (BSI).

Methods
This multicentre, retrospective cohort study analysed data from 14 public hospitals in Italy, including all consecutive adult patients admitted during 2021–2022 with septic shock due to P. aeruginosa BSI. We compared the outcomes of patients receiving AECT to those on adequate empirical monotherapy (AEMT) using Cox regression analyses.

Results
Of the 98 patients who received adequate empirical antibiotic treatment for septic shock due to P. aeruginosa BSI, 24 underwent AECT and 74 were given AEMT. AECT was associated with a lower 30-day all-cause mortality (25%, six out of 24) compared to AEMT (56.8%, 42 out of 74; P = 0.007). Multivariate Cox regression analysis indicated AECT as the only factor significantly associated with improved survival (aHR 0.30; 95% CI 0.12–0.71; P = 0.006). By contrast, the use of monotherapy or combination therapy in the definitive regimen did not influence mortality (aHR 0.73; 95% CI 0.25–2.14; P = 0.568).

Conclusions
AECT may be associated with reduced mortality compared to monotherapy in septic shock patients due to P. aeruginosa BSI. However, the administration of definitive adequate monotherapy or combination therapy yields similar outcomes, suggesting that once susceptibility is documented, switching to a single active in vitro drug is safe and feasible. Further studies are recommended to validate these findings.
Activity of antibiotics against Burkholderia cepacia complex in artificial sputum medium
Authors: Shukla Anusha , Rodriguez Shade , Brennan-Krohn Thea 
Published: September 2024

Abstract

Background
Burkholderia cepacia complex (Bcc) is a collection of intrinsically drug-resistant Gram-negative bacteria that cause life-threatening disease in people with cystic fibrosis (CF). Standard antimicrobial susceptibility testing methods have poor predictive value for clinical outcomes in Bcc infections, probably due in part to differences between in vitro testing conditions and the environment in which Bcc grow in the lungs of people with CF.

Objectives
To compare the activity of commonly used antibiotics under standard in vitro testing conditions with activity in conditions mimicking those found in vivo.

Methods
Two Bcc strains were grown alone and with six different antibiotics (minocycline, ceftazidime, meropenem, tobramycin, levofloxacin, trimethoprim-sulfamethoxazole) in two different media: standard cation-adjusted Mueller–Hinton broth and an artificial sputum medium designed to simulate the environment in the lungs of people with CF through addition of components including mucin, free DNA and amino acids. Two different starting conditions were used for time–kill assays: a standard ∼5 × 106 cfu/mL inoculum, and a high-density inoculum in which bacteria were grown for 72 hours before addition of antibiotics. Growth detection was performed by colony enumeration and by detection of resazurin reduction.

Results
There were major discrepancies between standard susceptibility results and activity in our models. Some antibiotics, including ceftazidime, showed minimal activity in all time–kill assays despite low minimal inhibitory concentrations, while others, notably tobramycin, were more active in high-density growth conditions than in standard time–kill assays.

Conclusions
This work underscores the urgent need to develop more clinically relevant susceptibility testing approaches for Bcc.
Bacterial persistence to antibiotics activated by tRNA mutations
Authors: Park Jongwook , Lee Dongju , Yi Hyojeong , Yun Cheol-Won , Kim Heenam Stanley 
Published: September 2024

Abstract

Objectives
Bacterial persistence is a significant cause of the intractability of chronic and relapsing infections. Despite its importance, many of the underlying mechanisms are still not well understood.

Methods
Antibiotic-tolerant mutants of Burkholderia thailandensis were isolated through exposure to lethal doses of AMP or MEM, followed by whole-genome sequencing to identify mutations. Subsequently, these mutants underwent comprehensive characterization via killing curves, growth curves, and persistence-fraction plots. Northern blot analysis was employed to detect uncharged tRNA, while the generation of relA and spoT null mutations served to confirm the involvement of the stringent response in this persistence mechanism. Phenotypic reversion of the persistence mutation was demonstrated by incubating the mutants without antibiotics for 2 weeks.

Results
We have discovered a novel mechanism of persistence triggered by specific mutations at positions 32 or 38 within the anticodon loop of tRNAAsp. This leads to heightened persistence through a RelA-dependent stringent response. Notably, this persistence can be easily reverted to wild-type physiology by losing the mutant tRNA allele within the tRNA gene cluster when persistence is no longer essential for survival.

Conclusions
This distinct form of persistence underscores the novel function of tRNA mutations at positions 32 or 38 within the anticodon loop, as well as the significance of the tRNA gene cluster in conferring adaptability to regulate persistence for enhanced survival.
Foundation model-driven distributed learning for enhanced retinal age prediction
Authors: Nielsen Christopher , Souza Raissa , Wilms Matthias , Forkert Nils D 
Published: September 2024

Abstract

Objectives
The retinal age gap (RAG) is emerging as a potential biomarker for various diseases of the human body, yet its utility depends on machine learning models capable of accurately predicting biological retinal age from fundus images. However, training generalizable models is hindered by potential shortages of diverse training data. To overcome these obstacles, this work develops a novel and computationally efficient distributed learning framework for retinal age prediction.

Materials and Methods
The proposed framework employs a memory-efficient 8-bit quantized version of RETFound, a cutting-edge foundation model for retinal image analysis, to extract features from fundus images. These features are then used to train an efficient linear regression head model for predicting retinal age. The framework explores federated learning (FL) as well as traveling model (TM) approaches for distributed training of the linear regression head. To evaluate this framework, we simulate a client network using fundus image data from the UK Biobank. Additionally, data from patients with type 1 diabetes from the UK Biobank and the Brazilian Multilabel Ophthalmological Dataset (BRSET) were utilized to explore the clinical utility of the developed methods.

Results
Our findings reveal that the developed distributed learning framework achieves retinal age prediction performance on par with centralized methods, with FL and TM providing similar performance (mean absolute error of 3.57 ± 0.18 years for centralized learning, 3.60 ± 0.16 years for TM, and 3.63 ± 0.19 years for FL). Notably, the TM was found to converge with fewer local updates than FL. Moreover, patients with type 1 diabetes exhibited significantly higher RAG values than healthy controls in all models, for both the UK Biobank and BRSET datasets (P &lt; .001).

Discussion
The high computational and memory efficiency of the developed distributed learning framework makes it well suited for resource-constrained environments.

Conclusion
The capacity of this framework to integrate data from underrepresented populations for training of retinal age prediction models could significantly enhance the accessibility of the RAG as an important disease biomarker.
Cost of medical care for malignant brain tumors at hospitals in the Japan Clinical Oncology Group brain-tumor study group
Authors: Motomura Kazuya , Sasaki Keita , Sugii Narushi , Yamaguchi Shigeru , Inoue Hirotaka , Oshima Akito , Tanaka Kazuhiro , Otani Yoshihiro , Shirahata Mitsuaki , Shibahara Ichiyo , Nagane Motoo , Tsuzuki Shunsuke , Matsutani Tomoo , Tsukamoto Yoshihiro , Kijima Noriyuki , Asano Kenichiro , Ohno Makoto , Inoue Akihiro , Mineharu Yohei , Miyake Keisuke , Mitobe Yuta , Hanihara Mitsuto , Kawanishi Yu , Deguchi Shoichi , Saito Masato , Matsuda Ryosuke , Ujifuku Kenta , Arita Hideyuki , Sato Yuichi , Yamashita Shinji , Yonezawa Ushio , Yamaguchi Junya , Momii Yasutomo , Ogawa Takahiro , Kambe Atsushi , Ohba Shigeo , Fukai Junya , Saito Norihiko , Kinoshita Masashi , Sumi Koichiro , Otani Ryohei , Uzuka Takeo , Takebe Noriyoshi , Koizumi Shinichiro , Saito Ryuta , Arakawa Yoshiki , Narita Yoshitaka ,   the Members of Japan Clinical Oncology Group Brain Tumor Study Group (JCOG-BTSG)
Published: September 2024

Abstract

Background
This study aimed to investigate what treatment are selected for malignant brain tumors, particularly glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL), in real-world Japan and the costs involved.

Methods
We conducted a questionnaire survey regarding treatment selections for newly diagnosed GBM and PCNSL treated between July 2021 and June 2022 among 47 institutions in the Japan Clinical Oncology Group-Brain Tumor Study Group. We calculated the total cost and cost per month of the initial therapy for newly diagnosed GBM or PCNSL.

Results
The most used regimen (46.8%) for GBM in patients aged ≤74 years was ‘Surgery + radiotherapy concomitant with temozolomide’. This regimen’s total cost was 7.50 million JPY (Japanese yen). Adding carmustine wafer implantation (used in 15.0%), TTFields (used in 14.1%), and bevacizumab (BEV) (used in 14.5%) to the standard treatment of GBM increased the cost by 1.24 million JPY for initial treatment, and 1.44 and 0.22 million JPY per month, respectively. Regarding PCNSL, ‘Surgery (biopsy) + rituximab, methotrexate, procarbazine, and vincristine (R-MPV) therapy’ was the most used regimen (42.5%) for patients of all ages. This regimen incurred 1.07 million JPY per month. The three PCNSL regimens based on R-MPV therapy were in ultra-high-cost medical care (exceeding 1 million JPY per month).

Conclusions
Treatment of malignant brain tumors is generally expensive, and cost-ineffective treatments such as BEV are frequently used. We believe that the results of this study can be used to design future economic health studies examining the cost-effectiveness of malignant brain tumors.
Real-world safety of nivolumab in patients with malignant pleural mesothelioma in Japan: post-marketing surveillance study
Authors: Fujimoto Nobukazu , Akamatsu Ayumi , Honda Chikara , Aoki Miki , Ohe Yuichiro 
Published: September 2024

Abstract

Objective
This post-marketing surveillance (PMS) was conducted to evaluate the incidence of adverse events with nivolumab in patients with unresectable, advanced or recurrent malignant pleural mesothelioma (MPM) that had progressed after first-line chemotherapy and to identify factors that potentially affected its safety in real-world clinical practice.

Methods
Patients who had not received nivolumab previously were registered between November 2018 and February 2021. Nivolumab was given intravenously 240 mg every 2 weeks or 480 mg every 4 weeks. Patients were followed up for 6 months after treatment initiation. Information on patient characteristics, treatment status, and adverse events was collected.

Results
This PMS enrolled 124 patients, involving 48 sites across Japan. At 6 months, nivolumab therapy was ongoing in 35.5% of patients (44/124) and had been discontinued in 64.5% (80/124). The overall incidence of treatment-related adverse events (TRAEs) was 40.3%; the incidence of Grade 3 or higher TRAEs was 12.9%. The pattern of TRAEs based on System Organ Class categories was generally consistent with those seen in the Japanese phase II MERIT study. The most common Grade 3 or higher TRAEs were interstitial lung disease (2.4%), lung disorder, and diarrhea (each 1.6%). The incidence of TRAEs was significantly higher in inpatients or patients who had good PS, high bodyweight, high body mass index, or autoimmune diseases than in those without these characteristics.

Conclusion
The post-marketing incidence of TRAEs with nivolumab in patients with MPM has been evaluated, and no new safety signals were identified compared to the phase II clinical trial in Japan.
Future Lives and Deaths with Purpose: Perspectives on Capacity, Character, and Intent
Authors: Maples Caitlin 
Published: September 2024

AbstractThe articles in this issue of the Journal of Medicine and Philosophy explore emerging technologies, medical innovations, and shifting moral norms, expanding present discussions around topics in bioethics both old and new. Some question whether novel definitions of death and harm change the moral permissibility of killing, particularly at the hands of a physician. Others question how increased or decreased abilities affect responsibility and achievement. Another illustrates how rhetorical appeals to character have been used to justify otherwise morally illicit actions within the clinic. Together, these articles shed new light on topics in the field of bioethics.
ID Consultant: Laboratory Monitoring During Long-Term Use of Oral Antimicrobials in Pediatric Patients
Authors: Downes Kevin J , Alemayehu Tinsae , Ashkenazi-Hoffnung Liat 
Published: September 2024

Abstract
Oral antimicrobials remain the mainstay of long-term treatment for many infections. Meanwhile, the use of oral agents is becoming commonplace for the treatment of several pediatric infections once managed exclusively with parenteral therapies. Unfortunately, antimicrobials are associated with several laboratory toxicities, particularly when high doses or combination therapies are used, but there is a paucity of data on optimal laboratory monitoring strategies. In this ID Consultant article, we offer a summary of the 3 most common laboratory-based toxicities seen with long-term use of oral antimicrobials—drug-induced kidney injury, liver injury, and hematological toxicities—and we provide our recommended approach to monitoring.
Linear β-1,2-glucans trigger immune hallmarks and enhance disease resistance in plants
Authors: Fuertes-Rabanal María , Largo-Gosens Asier , Fischer Alicia , Munzert Kristina S , Carrasco-López Cristian , Sánchez-Vallet Andrea , Engelsdorf Timo , Mélida Hugo 
Published: September 2024

Abstract
Immune responses in plants are triggered by molecular patterns or elicitors, recognized by plant pattern recognition receptors. Such molecular patterns are the consequence of host–pathogen interactions, and the response cascade activated after their perception is known as pattern-triggered immunity (PTI). Glucans have emerged as key players in PTI, but the ability of certain glucans to stimulate defensive responses in plants remains understudied. This work focused on identifying novel glucan oligosaccharides as molecular patterns. The ability of various microorganism-derived glucans to trigger PTI responses was tested, revealing that specific microbial-derived molecules, such as short linear β-1,2-glucans, trigger this response in plants by increasing the production of reactive oxygen species (ROS), mitogen-activated protein kinase phosphorylation, and differential expression of defence-related genes in Arabidopsis thaliana. Pre-treatments with β-1,2-glucan trisaccharide (B2G3) improved Arabidopsis defence against bacterial and fungal infections in a hypersusceptible genotype. The knowledge generated was then transferred to the monocotyledonous model species maize and wheat, demonstrating that these plants also respond to β-1,2-glucans, with increased ROS production and improved protection against fungal infections following B2G3 pre-treatments. In summary, as with other β-glucans, plants perceive β-1,2-glucans as warning signals which stimulate defence responses against phytopathogens.