bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety analysis by treatment periods from EMERALD-1: A phase 3, randomized, placebo-controlled study of transarterial chemoembolization with durvalumab with/without bevacizumab in participants with embolization-eligible unresectable hepatocellular carcinoma.
Authors: Chan Stephen Lam , Sangro Bruno , Kudo Masatoshi , Erinjeri Joseph P. , Qin Shukui , Ren Zhenggang , Arai Yasuaki , Breder Valeriy Vladimirovich , Lin Shi-Ming , Peron Jean-Marie , Nguyen Tien Quang , Yan Lunan , Chiu Chang-Fang , Santos Florinda A. , Veluvolu Anil , Thungappa Satheesh Chiradoni , Morgan Claire , Parsons Kerry , Xynos Ioannis , Lencioni Riccardo 
Published: June 2024

4122 Background: The global Phase 3 EMERALD-1 study (NCT03778957) primary endpoint was met: durvalumab (D) + bevacizumab (B) + transarterial chemoembolization (TACE) significantly improved progression-free survival vs placebos (pbos)+TACE (median 15.0 vs 8.2 mo; HR 0.77; 95% CI 0.61–0.98; p=0.032 [threshold 0.0435]) in participants (pts) with embolization-eligible unresectable hepatocellular carcinoma (uHCC) with a manageable safety profile. This post hoc, exploratory analysis assessed safety in the study’s 2 treatment (tx) periods (pds): D-TACE (D-T) and D-B. Methods: Pts were randomized 1:1:1 to D+TACE, D+B+TACE, or pbos+TACE. In the D-T pd, pts received 1–4 TACE (cTACE or DEB-TACE [investigator choice]) plus D (1500 mg Q4W) or pbo for D. In the D-B pd, post-last TACE, pts received D (1120 mg Q3W) plus pbo for B, D (1120 mg Q3W) plus B (15 mg/kg Q3W), or pbos for D and B. Adverse events (AEs), start/end date, maximum/change in CTCAE grade, and causality were assessed in the D-T and D-B pds in pts who received any study tx in the arm to which they were randomized, until end of follow-up. Results: The Table shows duration of exposure (DoE). In the D+TACE, D+B+TACE, and pbos+TACE arms, AEs were reported by 144 (74.6%), 139 (72.0%), and 148 (74.0%) pts in the D-T pd and 133 (68.9%), 147 (76.2%), and 132 (66.0%) pts in the D-B pd; were possibly related (pos rel) to study tx in 59 (30.6%), 56 (29.0%), and 41 (20.5%) pts in the D-T pd and 76 (39.4%), 114 (59.1%), and 69 (34.5%) pts in the D-B pd; and were provoked by TACE in 72 (37.3%), 90 (46.6%), and 85 (42.5%) pts in the D-T pd and 16 (8.3%), 18 (9.3%), and 21 (10.5%) pts in the D-B pd, respectively. Conclusions: D+B+TACE had a manageable safety profile across the D-T and D-B pds, consistent with the individual agents and underlying disease. These data further support D+B+TACE as a new potential standard of care in embolization-eligible uHCC. Clinical trial information: NCT03778957 . [Table: see text]
Severe Hypertriglyceridemia in a Patient With Metabolic Syndrome and Psoriasis on Risankizumab-Rzaa
Authors: Abdulwadood Isra , De melo Jose F , Scheel Robert C , Bois John P 
Published: June 2024

Abstract
We report a case of severe hypertriglyceridemia (HTG) complicated by hyperviscosity syndrome as a possible adverse reaction to risankizumab-rzaa in a 49-year-old male with a history of longstanding uncontrolled type 2 diabetes, obesity, and coronary artery disease with prior ST-elevation myocardial infarction. On admission, the patient presented with xanthomatous plaques, chest and epigastric discomfort, and headache. Subsequent blood testing revealed severely elevated triglyceride (TG) levels at 7670 mg/dL (86.59 mmol/L) [reference range: &lt;150 mg/dL; 1.69 mmol/L] and total cholesterol at 934 mg/dL (24.14 mmol/L) [reference range: &lt;200 mg/dL; 5.17 mmol/L]. Triglyceride levels decreased and symptoms resolved with dietary restrictions and plasmapheresis. At follow-up, his TG remained elevated but improved, and he was advised to continue lipid-lowering medications as well as cessation of risankizumab. While the patient presented with high risk factors, we posit that the subacute presentation of severe HTG is a possible result of his recent course of risankizumab-rzaa therapy for management of psoriasis. This is noteworthy as pharmaceutical surveys and clinical trials do not list severe HTG as an adverse effect. Postmarketing surveillance studies are essential to confirm this potential association and monitor drug safety. In summary, this case highlights a possible link between risankizumab and severe HTG, emphasizing the importance of ongoing pharmacovigilance to identify and manage unexpected adverse effects associated with new medications.
A Diagnosis of Turner Syndrome in the Eighth Decade of Life
Authors: Kaur Ruveena , O’Sullivan Susannah 
Published: June 2024

Abstract
Turner syndrome (TS) is the most common sex chromosome disorder affecting females and is usually diagnosed within the first 3 decades of life. It can present with primary amenorrhea or infertility and often has a typical phenotype, with associated medical conditions that require lifelong surveillance. We report the case of a 76-year-old female with a history of osteoporosis and vertebral fractures who presented to our specialist osteoporosis clinic following a neck of femur fracture. She revealed a history of short stature and primary amenorrhea as a young woman, with limited investigation and treatment. Her other medical history included coeliac disease, hypertension, and hearing and vision abnormalities. Given her phenotype, the patient was referred for a karyotype at age 76, which was consistent with mosaic TS (45, X in 78% of cells and 46, X, r(Y) in the remaining cells). We review reports of other cases of marked delay in TS diagnosis and discuss the consequences of a late diagnosis.
A Tune of Two Cities
Authors: Shadel Kevin 
Published: June 2024

Abstract
In the worst of times, the best of tunes. Or so might say singer Kim Hae-song (1910–195?), whose 1938 hit recording “Flowery Seoul” (“Kkot sŏul”) arguably offered more than a mere tongue-in-cheek retort to Fujiyama Ichirō’s (1911–1993) own 1936 “Tokyo Rhapsody” (“Tōkyō rapusodi”) by crooning in the Korean language over Koga Masao's (1904–1978) original composition. While both vocalists posture competitively with regard to the modern merits of their respective metropolises, the dark timbre of geopolitics dampens the otherwise playful interaction between these two popular songs, one by an imperial Japanese citizen, the other a colonial Korean subject. This article traces interwar popular music's regional, linguistic, and affective transposability to consider how the exceptional textual and melodic identity between Kim's and Fujiyama's respective city songs belies a more fundamental interpellation of Korean subjects into the transregional logic of Japanese Empire.
Nighttime Treatment of Ruptured Intracranial Aneurysms Are Associated With Poor Outcomes
Authors: Dumot Chloe , Gasimov Turab , Hatipoglu Majernik Gokce , Gurbuz Mehmet Sabri , Erginoglu Ufuk , Keles Abdullah , Arat Anil , Baskaya Mustafa K. 
Published: June 2024

BACKGROUND AND OBJECTIVES:
Rebleeding of ruptured intracranial aneurysms (RIA) is associated with poor outcomes. Although immediate treatment of RIAs is preferred, optimal treatment timing is multifactorial and may be a complicating factor for achieving the best outcomes. The objective of this study was to compare outcomes for patients with RIAs as a function of treatment time of day. To the best of our knowledge, this is the first study that examines how treatment time of day influences treatment outcomes.

METHODS:
This retrospective single-center study included all patients who were treated, either surgically or endovascularly, for RIAs within 24 hours after admission. Exclusion criteria were blister, mycotic or giant aneurysms, or incomplete records. The modified Rankin Scale was used to evaluate treatment outcomes using multivariate analysis. Nighttime treatment was defined when greater than 50% of the procedure was performed between 10 pm and 7 am, with other times classified as daytime treatment. Off-hours treatment was defined when more than 50% of the procedure was performed between 7 pm and 7 am, with other times classified as on-hours.

RESULTS:
This study included 493 patients, with 84.2% (415) treated during the daytime, 15.8% (78) during the nighttime, 67.5% (333) during on-hours, and 32.5% (160) during off-hours. These groups did not differ according to age, sex, World Federation of Neurosurgical Societies and Fisher scales, aneurysm size, location, and surgical or endovascular treatment. Outcomes were favorable (modified Rankin Scale 0-2) for 72.0% (299) of patients treated during the daytime and 60.0% (46) of patients treated during the nighttime. Aneurysm treatment during the nighttime (OR: 0.50 [95% CI: 0.28-0.91], P = .023) but not during off-hours (OR: 0.76 [0.50-1.14], P = .18) was independently associated with unfavorable outcomes.

CONCLUSION:
Nighttime treatment was associated with poorer outcomes. Further studies are needed to evaluate outcomes if treatment is postponed to daytime hours.
Contribution of Streptococcus pseudopneumoniae and Streptococcus salivarius to vocal fold mucosal integrity and function
Authors: Lungova Vlasta , Gowda Madhu , Fernandez Jessica M. , Bartley Stephanie , Venkatraman Anumitha , Rey Federico E. , Thibeault Susan L. 
Published: June 2024

ABSTRACT
Structural changes to the vocal fold (VF) epithelium, namely, loosened intercellular junctions, have been reported in VF benign lesions. The potential mechanisms responsible for the disruption of cell junctions do not address the contribution of resident microbial communities to this pathological phenomenon. In this study, we focused on determining the relationship between Streptococcus pseudopneumoniae (SP), a dominant bacterial species associated with benign lesions, and Streptococcus salivarius (SS), a commensal bacterium, with human VF epithelial cells in our three-dimensional model of the human VF mucosa. This experimental system enabled direct deposition of bacteria onto constructs at the air/liquid interface, allowing for the assessment of bacterium–host interactions at the cellular, molecular and ultrastructural levels. Our findings demonstrate that SP disrupts VF epithelial integrity and initiates inflammation via the exported products HtrA1 and pneumolysin. In contrast, SS attaches to the VF epithelium, reduces inflammation and induces Mmp2-mediated apical desquamation of infected cells to mitigate the impact of pathogens. In conclusion, this study highlights the complexity of microbial involvement in VF pathology and potential VF mucosal restoration in the presence of laryngeal commensals.
Muscle-specific lack of Gfpt1 triggers ER stress to alleviate misfolded protein accumulation
Authors: Zhang Ruchen , Farshadyeganeh Paniz , Ohkawara Bisei , Nakajima Kazuki , Takeda Jun-ichi , Ito Mikako , Zhang Shaochuan , Miyasaka Yuki , Ohno Tamio , Mori-Yoshimura Madoka , Masuda Akio , Ohno Kinji 
Published: June 2024

ABSTRACT
Pathogenic variants in GFPT1, encoding a key enzyme to synthesize UDP-N-acetylglucosamine (UDP-GlcNAc), cause congenital myasthenic syndrome (CMS). We made a knock-in (KI) mouse model carrying a frameshift variant in Gfpt1 exon 9, simulating that found in a patient with CMS. As Gfpt1 exon 9 is exclusively expressed in striated muscles, Gfpt1-KI mice were deficient for Gfpt1 only in skeletal muscles. In Gfpt1-KI mice, (1) UDP-HexNAc, CMP-NeuAc and protein O-GlcNAcylation were reduced in skeletal muscles; (2) aged Gfpt1-KI mice showed poor exercise performance and abnormal neuromuscular junction structures; and (3) markers of the unfolded protein response (UPR) were elevated in skeletal muscles. Denervation-mediated enhancement of endoplasmic reticulum (ER) stress in Gfpt1-KI mice facilitated protein folding, ubiquitin-proteasome degradation and apoptosis, whereas autophagy was not induced and protein aggregates were markedly increased. Lack of autophagy was accounted for by enhanced degradation of FoxO1 by increased Xbp1-s/u proteins. Similarly, in Gfpt1-silenced C2C12 myotubes, ER stress exacerbated protein aggregates and activated apoptosis, but autophagy was attenuated. In both skeletal muscles in Gfpt1-KI mice and Gfpt1-silenced C2C12 myotubes, maladaptive UPR failed to eliminate protein aggregates and provoked apoptosis.
The Association of Mismatch Repair Status with Microscopically Positive (R1) Margins in Stage III Colorectal Cancer: A Retrospective Cohort Study
Authors: Smith Henry G. , Schlesinger Nis H. , Chiranth Deepthi , Qvortrup Camilla 
Published: June 2024

Abstract
Background
There is mounting evidence that microscopically positive (R1) margins in patients with colorectal cancer (CRC) may represent a surrogate for aggressive cancer biology rather than technical failure during surgery. However, whether detectable biological differences exist between CRC with R0 and R1 margins is unknown. We sought to investigate whether mismatch repair (MMR) status differs between Stage III CRC with R0 or R1 margins.

Methods
Patients treated for Stage III CRC from January 1, 2016 to December 31, 2019 were identified by using the Danish Colorectal Cancer Group database. Patients were stratified according to MMR status (proficient [pMMR] vs. deficient [dMMR]) and margin status. Outcomes of interest included the R1 rate according to MMR and overall survival.

Results
A total of 3636 patients were included, of whom 473 (13.0%) had dMMR colorectal cancers. Patients with dMMR cancers were more likely to be elderly, female, and have right-sided cancers. R1 margins were significantly more common in patients with dMMR cancers (20.5% vs. 15.2%, p < 0.001), with the greatest difference seen in the rate of R1 margins related to the primary tumour (8.9% vs. 4.7%) rather than to lymph node metastases (11.6% vs. 10.5%). This association was seen in both right- and left-sided cancers. On multivariable analyses, R1 margins, but not MMR status, were associated with poorer survival, alongside age, pN stage, perineural invasion, and extramural venous invasion.

Conclusions
In patients with Stage III CRC, dMMR status is associated with increased risks of R1 margins following potentially curative surgery, supporting the use of neoadjuvant immunotherapy in this patient group.
Exploring barriers to care home research recruitment during the COVID-19 pandemic: The influence of social media recruitment posts and public sentiment
Authors: Schoultz Mariyana , Mcgrogan Claire , Carolan Clare , Macaden Leah , Beattie Michelle 
Published: June 2024

Introduction
Recruitment of care home staff to research studies is recognised as challenging. This was further exacerbated by the COVID-19 pandemic and the associated negative media portrayal of care home workers. Social media use has surged since the onset of COVID-19 lockdowns, offering a plausible approach to understanding the barriers to care home research recruitment and gaining insight into public perceptions of care home workers.

Aim
To utilise comments from two Facebook recruitment posts to: 1) gain an understanding of potential barriers to recruitment of healthcare workers (HCWs) in UK care homes, and 2) explore public sentiment towards care home research and care homes in the context of the COVID-19 pandemic.

Methods
This cross-sectional study analysed comments from two Facebook posts (available June-October 2021) advertising a separate study on psychological support for care staff during the pandemic. This study was situated within a larger investigation into the mental health and wellbeing of care home staff and employed both qualitative analysis and quantitative methods (word count and correlations between words used and between posts).

Results
Three themes were identified from the qualitative analysis: support, mistrust and blame. There was a greater use of words associated with support and negative emotive words in post 2. Post 2 comments featured significantly more choice words and first-person singular pronouns than post 1 which indicated a resentful sentiment from those who advocate freedom of choice and control. Discussion of mistrust towards researchers was most prominent in post 1 indicating the importance of relationship building between researchers and HCWs in UK care homes. With attribution to blame, there was a larger range of negative emotion words than positive emotion words.

Discussion and conclusion
Taken together our findings offer novel insights into why recruitment to care home research during the pandemic including the use of social media might be problematic. Social media is a useful tool for recruitment but should not be considered as a one-time input. Researchers should pro-actively engage with the study population from the start using co-design with resident and public groups to support recruitment and ensure these populations are accurately represented within research.
The effect of multi-component exercise on cognition function in patients with diabetes: A systematic review and meta-analysis
Authors: Sun Zhiyuan , Liu Hualei , Yan Min , Zeng Haiqing , Hu Yiping , Tian Xuewen , Mao Dewei 
Published: June 2024

Background
This meta-analysis investigated the influence of exercise on cognitive function in people living with diabetes.

Methods
Stringent criteria for literature inclusion and exclusion were defined. Searches were conducted across four English databases to gather randomized controlled trials investigating exercise interventions for cognitive function in people living with diabetes. Outcome indicators from 1193 subjects across 12 articles were analyzed using RevMan 5.4 software.

Results
Exercise intervention demonstrated the ability to mitigate cognitive decline in people living with diabetes, with a combined effect size (standardized mean difference) of 0.91, 95% CI: 0.28, 1.54, P < 0.00001. The intervention effect showed significant modulation by intervention content (I2 = 95%), intervention duration (I2 = 95%), intervention frequency (I2 = 95%), and intervention cycle (I2 = 96%). Among these factors, multi-component exercise, sessions >40 minutes, exercise frequency >4 times per week, and sustained exercise for >6 months were paramount, all with P < 0.05.

Conclusion
Exercise intervention emerges as a viable strategy for delaying cognitive decline in people living with diabetes. Its efficacy is subject to modulation by various variables. Optimal intervention includes multi-component exercise, individual sessions lasting 40–60 minutes, exercising >4 times a week, and continuous exercise for over 6 months.
Influence of selected non-antibiotic pharmaceuticals on antibiotic resistance gene transfer in Escherichia coli
Authors: Mohamed Doaa Safwat , Abd El-Baky Rehab Mahmoud , El-Mokhtar Mohamed Ahmed , Ghanem Sahar K. , Yahia Ramadan , Alqahtani Alaa M. , Abourehab Mohammed A. S. , Ahmed Eman Farouk 
Published: June 2024

Background
Antibiotic resistance genes (ARGs) transfer rapidly among bacterial species all over the world contributing to the aggravation of antibiotic resistance crisis. Antibiotics at sub-inhibitory concentration induce horizontal gene transfer (HRT) between bacteria, especially through conjugation. The role of common non-antibiotic pharmaceuticals in the market in disseminating antibiotic resistance is not well studied.

Objectives
In this work, we indicated the effect of some commonly used non-antibiotic pharmaceuticals including antiemetic (metoclopramide HCl) and antispasmodics (hyoscine butyl bromide and tiemonium methyl sulfate) on the plasmid-mediated conjugal transfer of antibiotic resistance genes between pathogenic E. coli in the gastric intestinal tract (GIT).

Methods
Broth microdilution assay was used to test the antibacterial activity of the tested non-antibiotic pharmaceuticals. A conjugation mating system was applied in presence of the studied non-antibiotic pharmaceuticals to test their effect on conjugal transfer frequency. Plasmid extraction and PCR were performed to confirm the conjugation process. Transmission electron microscopy (TEM) was used for imaging the effect of non-antibiotic pharmaceuticals on bacterial cells.

Results
No antibacterial activity was reported for the used non-antibiotic pharmaceuticals. Plasmid-mediated conjugal transfer between isolates was induced by metoclopramide HCl but suppressed by hyoscine butyl bromide. Tiemonium methylsulfate slightly promoted conjugal transfer. Aggregation between cells and periplasmic bridges was clear in the case of metoclopramide HCl while in presence of hyoscine butyl bromide little affinity was observed.

Conclusion
This study indicates the contribution of non-antibiotic pharmaceuticals to the dissemination and evolution of antibiotic resistance at the community level. Metoclopramide HCl showed an important role in the spread of antibiotic resistance.
The Modified Ambiguity Function Approach with regularization for instantaneous precise GNSS positioning
Authors: Fischer Artur , Cellmer Sławomir , Nowel Krzysztof 
Published: June 2024

Abstract
The Modified Ambiguity Function Approach (MAFA) implicitly conducts the search procedure of carrier phase GNSS integer ambiguity resolution (IAR) in the coordinate domain using the integer least squares (ILS) principle, i.e. MAFA-ILS. One of the still open scientific problems is an accurate definition of the search region, especially in the context of instantaneous IAR. In doing so, the float solution results, which encompass float position (FP) and its variance-covariance (VC) matrix, must be improved as these are necessary for defining the search region. For this reason, the ambiguity parameters are separately regularized, and then the baseline parameters are conditioned on regularized float ambiguities. The conditional-regularized estimation is thus designed, obtaining the regularized FP (RFP) and its VC-matrix. This solution is promising because its accuracy is enhanced in the sense of mean squared error (MSE) thanks to the improved precision at the cost of regularized bias. The optimal regularization parameter (RP) values obtained for ambiguity parameters balance the contributions of improved precision and bias in the regularized float baseline solution’s MSE. Therefore, the regularized search region is defined accurately in the coordinate domain to contain such approximate coordinates that more frequently give the correct ILS solution. It also contains fewer MAFA-ILS candidates, improving the search procedure’s numerical efficiency. The regularized ILS estimator performs well with the presence of bias, increasing the probability of correct IAR in the coordinate domain.
Therapeutic ayurvedic interventions for the management of rheumatoid arthritis complicated by adhesive capsulitis – a case report
Authors: Khurana Bhavya , Dipankar Digambar G. , Saini Neha , Dubal Neha Suresh 
Published: June 2024

Abstract

Background
Rheumatoid Arthritis is an autoimmune disorder that leads to persistent symmetrical polyarthritis accompanied by systemic manifestations. It may lead to an array of deformities and even complications like rheumatoid nodules, carpal tunnel syndrome, adhesive capsulitis, cardiovascular diseases, and many more.

Objectives
This case report intends to discuss the ayurvedic management of Rheumatoid Arthritis which was complicated by Adhesive Capsulitis.

Methods
A 73-year-old male patient was diagnosed with Rheumatoid Arthritis. He had previously undergone allopathic treatment for a year. In June 2023, the patient sought ayurvedic treatment for his ailment and later acquired signs and symptoms of Adhesive Capsulitis. He was given ayurvedic oral medications along with external therapeutic procedures.

Results
There was a significant reduction in the values of the Routine Assessment of Patient Index Data 3 (RAPID3) score, Clinical Disease Activity Index (CDAI), Rheumatoid Factor (Quantitative), Visual Analogue Scale (VAS), and improvement in the range of movement of the affected joint.

Conclusions
Ayurvedic medicines are effective in managing Rheumatoid Arthritis along with the complication of Adhesive Capsulitis.