bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased risk of radiation pneumonitis with concurrent use of renin-angiotensin system inhibitors in thoracic radiation therapy of lung cancer
Authors: Zheng Yawen , Cong Changsheng , Wang Zewen , Liu Yanan , Zhang Mingyan , Zhou Hao , Su Chen , Sun Meili 
Published: October 2023

BackgroundRadiation pneumonitis (RP) is the primary dose-limiting toxicity associated with radiotherapy. This study aimed to observe the effects of renin-angiotensin system inhibitors in Chinese patients with lung cancer who received thoracic radiation.MethodsPatients with lung cancer who received thoracic radiation at a total dose of ≥45 Gray between October 2017 and December 2022 were enrolled in this study. We retrospectively evaluated the factors influencing grade 2 or higher RP.ResultsA total of 320 patients were enrolled in this study; 62 patients were identified as angiotensin receptor blockers or angiotensin-converting enzyme inhibitor users. Additionally, 99 patients (30.9%) had grade 2 or higher RP, and the incidence in the renin-angiotensin system inhibitor group was 17.7% (11 out of 62 patients). Patients in the renin-angiotensin system inhibitors (RASi) group were older and had a higher percentage of males, lower percentage of ECOG score 0, higher percentage of hypertension, and higher percentage of adenocarcinoma than those in the non-RASi group. ECOG score [hazard ratio (HR) = 1.69, p = 0.009], history of smoking (HR = 1.76, p = 0.049), mean dose (HR = 3.63, p = 0.01), and RASi (HR = 0.3, p = 0.003) were independent predictive factors for RP. All subgroups benefited from RASi.ConclusionThis study showed that oral RASi administration has the potential to mitigate the incidence of grade 2 or higher RP in patients with lung cancer undergoing thoracic radiotherapy. To validate and further substantiate these findings, additional prospective research is warranted.
Reducing the receipt of contraindicated medications in patients with Parkinson disease
Authors: Goldin Caroline , Sillau Stefan , Worledge Elisa , Bremmer Jarrett , Cummins Robbie , Tremolet de Villers Kathryn , Fullard Michelle E. 
Published: October 2023

BackgroundThe administration of antidopaminergic medications to patients with Parkinson’s disease (PD) can exacerbate symptoms, and in the hospital setting, can lead to complications and increased length of stay. Despite efforts to improve medication administration through provider education and patient-centered interventions, the problem persists, with an estimated 21–43% of hospitalized PD patients receiving dopamine blocking medications.MethodsIn this study, a best practice alert (BPA) was developed that was triggered when an antidopaminergic medication was ordered in the Emergency Department or hospital for a patient with a diagnosis of PD in the EMR. The primary outcomes were receipt of a contraindicated medication, length of stay (LOS) and readmission within 30 days. These outcomes were compared between the 12 months prior to the intervention and the 12 months post intervention. Data were also collected on admitting diagnosis, admitting service, neurology involvement and patient demographics.ResultsFor pre-intervention inpatient encounters, 18.3% involved the use of a contraindicated medication. This was reduced to 9.4% of all inpatient encounters for PD patients in the first 3 months post-intervention and remained lower at 13.3% for the full 12 months post-intervention. The overall rate of contraindicated medication use was low for ED visits at 4.7% pre-intervention and 5.7% post-intervention. Receipt of a contraindicated medication increased the risk of a longer length of stay, both before and after the intervention, but did not significantly affect 30-day readmission rate.ConclusionAn EMR BPA decreased the use of contraindicated medications for PD patients in the hospital setting, especially in the first 3 months. Strategies are still needed to reduce alert fatigue in order to maintain initial improvements.
Superior semicircular canal dehiscence and subsequent closure induces reversible impaired decision-making
Authors: Mowery Todd M. , Wackym P. Ashley , Nacipucha Jacqueline , Dangcil Evelynne , Stadler Ryan D. , Tucker Aaron , Carayannopoulos Nicolas L. , Beshy Mina A. , Hong Sean S. , Yao Justin D. 
Published: October 2023

BackgroundVestibular loss and dysfunction has been associated with cognitive deficits, decreased spatial navigation, spatial memory, visuospatial ability, attention, executive function, and processing speed among others. Superior semicircular canal dehiscence (SSCD) is a vestibular-cochlear disorder in humans in which a pathological third mobile window of the otic capsule creates changes to the flow of sound pressure energy through the perilymph/endolymph. The primary symptoms include sound-induced dizziness/vertigo, inner ear conductive hearing loss, autophony, headaches, and visual problems; however, individuals also experience measurable deficits in basic decision-making, short-term memory, concentration, spatial cognition, and depression. These suggest central mechanisms of impairment are associated with vestibular disorders; therefore, we directly tested this hypothesis using both an auditory and visual decision-making task of varying difficulty levels in our model of SSCD.MethodsAdult Mongolian gerbils (n = 33) were trained on one of four versions of a Go-NoGo stimulus presentation rate discrimination task that included standard (“easy”) or more difficult (“hard”) auditory and visual stimuli. After 10 days of training, preoperative ABR and c+VEMP testing was followed by a surgical fenestration of the left superior semicircular canal. Animals with persistent circling or head tilt were excluded to minimize effects from acute vestibular injury. Testing recommenced at postoperative day 5 and continued through postoperative day 15 at which point final ABR and c+VEMP testing was carried out.ResultsBehavioral data (d-primes) were compared between preoperative performance (training day 8–10) and postoperative days 6–8 and 13–15. Behavioral performance was measured during the peak of SSCD induced ABR and c + VEMP impairment and the return towards baseline as the dehiscence began to resurface by osteoneogenesis. There were significant differences in behavioral performance (d-prime) and its behavioral components (Hits, Misses, False Alarms, and Correct Rejections). These changes were highly correlated with persistent deficits in c + VEMPs at the end of training (postoperative day 15). The controls demonstrated additional learning post procedure that was absent in the SSCD group.ConclusionThese results suggest that aberrant asymmetric vestibular output results in decision-making impairments in these discrimination tasks and could be associated with the other cognitive impairments resulting from vestibular dysfunction.
Reversible cerebral vasoconstriction syndrome following intracranial hypotension in a postpartum patient: a case report and literature review
Authors: Li Shuhua , Yang Yi , Zuo Jiacai , Du Ningli , Kou Guoxian 
Published: October 2023

IntroductionReversible cerebral vasoconstriction syndrome (RCVS) is a potentially life-threatening neurological disorder, rarely linked to intracranial hypotension. The presentation showed a patient with intracranial hypotension after peridural anesthesia who experienced RCVS during the early postpartum period, suggesting a potential involvement of intracranial hypotension in RCVS occurrence.Case reportA young female of 29 years of age initially developed an orthostatic headache after undergoing a painless delivery with lumbar epidural anesthesia. Intracranial hypotension was considered the underlying cause. Her headache was partially resolved after intravenous fluid therapy and strict bed rest. After 2 days, the patient had a new onset thunderclap headache with generalized seizures, cortical blindness, and elevated blood pressure. An MRI scan revealed high signal intensity within the temporal, parietal, and occipital lobes, left caudate nucleus, and right cerebellum on T2-FLAIR imaging with vasogenic edema. MR angiography indicated multifocal, segmental, diffuse narrowing affecting the cerebral arteries that are large and medium. An RCVS2 score was six, and the patient was diagnosed with RCVS. She was managed conservatively, quickly improving her symptoms. After 10 days, a follow-up MRI indicated a significant reduction in the abnormal signal, and a substantial resolution of the constriction of the cerebral artery constriction was confirmed by MR angiography.ConclusionIntracranial hypotension could potentially lead to RCVS in postpartum patients, and it may be triggered by cerebral vasospasm secondary to intracranial hypotension.
High-definition transcranial direct current stimulation for upper extremity rehabilitation in moderate-to-severe ischemic stroke: a pilot study
Authors: Williamson Jordan N. , James Shirley A. , He Dorothy , Li Sheng , Sidorov Evgeny V. , Yang Yuan 
Published: October 2023

IntroductionPrevious studies found that post-stroke motor impairments are associated with damage to the lesioned corticospinal tract (CST) and hyperexcitability of the contralesional cortico-reticulospinal tract (CRST). This proof-of-concept study aims to develop a non-invasive brain stimulation protocol that facilitates the lesioned CST and inhibits the contralesional CRST to improve upper extremity rehabilitation in individuals with moderate-to-severe motor impairments post-stroke.MethodsFourteen individuals (minimum 3 months post ischemic stroke) consented. Physician decision of the participants baseline assessment qualified eight to continue in a randomized, double-blind cross-over pilot trial (ClinicalTrials.gov Identifier: NCT05174949) with: (1) anodal high-definition transcranial direct stimulation (HD-tDCS) over the ipsilesional primary motor cortex (M1), (2) cathodal HD-tDCS over contralesional dorsal premotor cortex (PMd), (3) sham stimulation, with a two-week washout period in-between. Subject-specific MR images and computer simulation were used to guide HD-tDCS and verified by Transcranial Magnetic Stimulation (TMS) induced Motor Evoked Potential (MEP). The motor behavior outcome was evaluated by an Fugl-Meyer Upper Extremity score (primary outcome measure) and the excitability of the ipslesoinal CST and contralesional CRST was determined by the change of MEP latencies and amplitude (secondary outcome measures).ResultsThe baseline ipsilesional M1 MEP latency and amplitude were correlated with FM-UE. FM-UE scores were improved post HD-tDCS, in comparison to sham stimulation. Both anodal and cathodal HD-tDCS reduced the latency of the ipsilesional M1 MEP. The contralesional PMd MEP disappeared/delayed after HD-tDCS.DiscussionThese results suggest that HD-tDCS could improve the function of the lesioned corticospinal tract and reduce the excitability of the contralesional cortico-reticulospinal tract, thus, improving motor function of the upper extremity in more severely impaired individuals.
1H-MRS neurometabolite profiles and motor development in school-aged children who are HIV-exposed uninfected: a birth cohort study
Authors: Williams Simone R. , Robertson Frances C. , Wedderburn Catherine J. , Ringshaw Jessica E. , Bradford Layla , Nyakonda Charmaine N. , Hoffman Nadia , Joshi Shantanu H. , Zar Heather J. , Stein Dan J. , Donald Kirsten A. 
Published: October 2023

ObjectiveAlterations in regional neurometabolite levels as well as impaired neurodevelopmental outcomes have previously been observed in children who are HIV-exposed uninfected (CHEU). However, little is known about how neurometabolite profiles may relate to their developmental impairment. This study aimed to compare neurometabolite concentrations in school-aged CHEU and children who are HIV-unexposed (CHU) and to explore associations of neurometabolite profiles with functional neurodevelopment in the context of perinatal HIV exposure.MethodsWe used 3 T single voxel proton magnetic resonance spectroscopy (1H-MRS) to quantify absolute and relative neurometabolites in the parietal gray and parietal white matter in school-aged CHEU and aged- and community-matched CHU. Functional neurodevelopmental outcomes were assessed using the early learning outcome measure (ELOM) tool at 6 years of age.ResultsOur study included 152 school-aged children (50% males), 110 CHEU and 42 CHU, with an average age of 74 months at the neuroimaging visit. In an adjusted multiple linear regression analysis, significantly lower glutamate (Glu) concentrations were found in CHEU as compared to CHU in the parietal gray matter (absolute Glu, p = 0.046; Glu/total creatine (Cr+PCr) ratios, p = 0.035) and lower total choline to creatine ratios (GPC+PCh/Cr+PCr) in the parietal white matter (p = 0.039). Using factor analysis and adjusted logistic regression analysis, a parietal gray matter Glu and myo-inositol (Ins) dominated factor was associated with HIV exposure status in both unadjusted (OR 0.55, 95% CI 0.17–0.45, p = 0.013) and adjusted analyses (OR 0.59, 95% CI 0.35–0.94, p = 0.031). With Ins as one of the dominating metabolites, this neurometabolic factor was similar to that found at the age of two years. Furthermore, this factor was also found to be correlated with ELOM scores of gross motor development in CHEU (Pearson’s r = −0.48, p = 0.044). In addition, in CHEU, there was a significant association between Ins/Cr+PCr ratios in the parietal white matter and ELOM scores of fine motor coordination and visual motor integration in CHEU (Pearson’s r = 0.51, p = 0.032).ConclusionReduced Glu concentrations in the parietal gray matter may suggest regional alterations in excitatory glutamatergic transmission pathways in the context of perinatal HIV and/or antiretroviral therapy (ART) exposure, while reduced Cho ratios in the parietal white matter suggest regional myelin loss. Identified associations between neurometabolite profiles and gross and fine motor developmental outcomes in CHEU are suggestive of a neurometabolic mechanism that may underlie impaired motor neurodevelopmental outcomes observed in CHEU.
Targeted isolation of natural analogs of anti-mycobacterial hit compounds based on the metabolite profiling of a large collection of plant extracts
Authors: Kirchhoffer Olivier Auguste , Nitschke Jahn , Allard Pierre-Marie , Marcourt Laurence , David Bruno , Grondin Antonio , Hanna Nabil , Queiroz Emerson Ferreira , Soldati Thierry , Wolfender Jean-Luc 
Published: October 2023

Antibiotics resistance is a clear threat to the future of current tuberculosis treatments like rifampicin, prompting the need for new treatment options in this field. While plants can offer a plethora of chemical diversity in their constitutive natural products to tackle this issue, finding potentially bioactive compounds in them has not always proven to be that simple. Classical bioactivity-guided fractionation approaches are still trendy, but they bear significant shortfalls, like their time-consuming nature as well as the ever-increasing risk of isolating known bioactive compounds. In this regard, we have developed an alternative method to the latter approach that allows for natural derivatives of a known bioactive scaffold to be efficiently targeted and isolated within a large library of plant extracts. Hence our approach allows for the anticipation of bioactive structure independently of preliminary bioassays. By relying on the chemical diversity of a set of 1,600 plant extracts analyzed by HRMS/MS, we were able to isolate and characterize several minor derivatives of a previously reported bioactive aza-anthraquinone compound from Cananga brandisiana, selected within the plant set. Assessment of bioactivity on these derivatives (especially onychine, with an IC50 value of 39 µM in infection) confirmed their expected activity on Mycobacterium marinum in our anti-infective assay. This proof-of-concept study has established an original path towards bioactive compounds isolation, with the advantage of potentially highlighting minor bioactive compounds, whose activity may not even be detectable at the extract level.
Health-related quality of life and patient-centred outcomes with COVID-19 vaccination in patients with breast cancer and gynaecological malignancies
Authors: Forster Marie , Wuerstlein Rachel , Koenig Alexander , Stefan Alexandra , Wiegershausen Elisa , Batz Falk , Trillsch Fabian , Mahner Sven , Harbeck Nadia , Chelariu-Raicu Anca 
Published: October 2023

IntroductionSafety and tolerability of COVID-19 vaccines were demonstrated by several clinical trials which led to the first FDA/EMA approvals in 2021. Because of mass immunizations, most social restrictions were waived with effects on quality of life. Therefore, our a-priori hypothesis was that COVID-19 vaccination impacted the health-related quality of life (HR-QoL) in patients with breast and gynecological cancer.MethodsFrom March 15th until August 11th, 2022, fully vaccinated patients with breast and gynecological cancer treated in the oncological outpatient clinics of the Department of Obstetrics and Gynecology, LMU University Hospital, Munich, Germany filled out a vaccine related QoL survey. Patients were asked about demographics (age, comorbidities), clinical parameters related to previous COVID-19 infections, and HR-QoL related parameters (living situation, responsibilities in everyday life). Subsequently, a questionnaire with 12 items was designed using a 5-point Likert scale (0 – strongly disagree/4 – strongly agree), covering the aspects health and therapy, social environment, participation in everyday life and overall assessment.ResultsBy August 11th, 2022, 108 out of 114 (94.7%) patients had received at least three doses of COVID-19 vaccine and six patients at least two doses. More than half of the surveyed patients were &gt;55y (52.6%; mean: 55.1y, range 29-86y). Patients with breast cancer (n= 83) had early (59.0%) or metastatic cancer (41.0%); gynecological cancers (n=31) also included metastatic (54.8%) and non-metastatic cancer (45.2%). 83.3% of the patients stated that COVID-19 vaccination had a positive impact on their HR-QoL. Furthermore, 29 patients (25.4%) had undergone a COVID-19 infection. These patients reported self-limiting symptoms for a median duration of 5.9 days and no hospital admissions were registered.ConclusionsOur study demonstrates that vaccination against COVID-19 was positively associated with HR-QoL in patients with breast and gynecological cancer. Furthermore, vaccinated patients who underwent COVID-19 disease experienced only self-limiting symptoms.
Molecular landscape and clinical significance of exon 11 mutations in KIT gene among patients with gastrointestinal stromal tumor: a retrospective exploratory study
Authors: Zhao Ruihua , An Tianqi , Liu Min , Zhou Yanan , Li Rui , Jiang Guozhong , Li Jing , Cao Xinguang , Zong Hong 
Published: October 2023

ObjectiveThis aim of this study was to investigate the prognostic significance of KIT exon 11 mutation subtypes in patients with GISTs.MethodsA total of 233 consecutive patients diagnosed with GISTs at the First Affiliated Hospital of Zhengzhou University from January 2013 to August 2018 were included in this study. The prevalence and mutation landscape of exon 11 in KIT was presented. The clinicopathological characteristics and prognosis among the different mutation subtypes were analyzed. All the statistical analyses were performed by SPSS22.0.ResultsSomatic mutational analysis indicated that point mutations were the most frequently detected mutations followed by deletions &amp; compound mutations and insertion and tandem duplication mutations in the stomach. Point mutations showed a low mitotic count and a high risk of recurrence, and deletions and compound mutations have a high mitotic count while insertions and tandem duplication mutations showed a low mitotic count with an intermediate recurrence risk. Point mutations and deletions frequently occurred in sequence region codons 550-560 of exon 11, while compound mutations, insertion, and tandem duplication were mainly detected in codons 557-559, 572-580, and 577-581, respectively. The multi-variation analysis demonstrated that tumor diameter and high recurrence risk groups had worse prognostic values. However, mutation types were not significant predictors of relapse-free survival (RFS) in GISTs. Survival analysis suggested no significant difference in RFS between the 557/558 deletion and the other deletions.ConclusionThis study suggested that mutations in exon 11 of the KIT gene were common with intermediate/high recurrence risk in GISTs patients. Tumor diameter ≥5 cm, and deletions mutations might predict a worse prognosis.
Case report: Thrombotic microangiopathy in pediatric multisystem inflammatory syndrome associated with COVID-19: a case series
Authors: Nalçacıoğlu Hülya , Önal H. Gözde , Bozkaya Yücel Burcu , Tekcan Karali Demet , Erdeniz Emine , Öz Tuncer Gökçen , Aydoğ Özlem 
Published: October 2023

IntroductionThis report provides insight into three distinct pediatric cases exhibiting a nexus between multisystem inflammatory syndrome in children (MIS-C) and thrombotic microangiopathy (TMA) triggered by COVID-19. The aim is to underscore the range of clinical presentations and the essentiality of early interventions.Case presentationsThis report presents three cases aged 10 months, 7 years, and 3 years with persistent fever, diarrhea, nausea, and vomiting. The first case, a 10-month-old girl, demonstrated acute kidney injury (AKI) and microangiopathic hemolytic anemia (MAHA) following a COVID-19 infection. Despite initial negative SARS-CoV-2 RT-PCR results, her condition escalated rapidly, presenting increased levels of LDH (peaking at 4,200 U/L) and requiring renal replacement therapy (RRT) to manage deteriorating renal function. Interventions with eculizumab and anakinra led to marked improvements, with a stable follow-up of 13 months post-hospitalization. The second case involved a 7-year-old girl who developed symptoms of MIS-C, hemolytic uremic syndrome (HUS), and posterior reversible encephalopathy syndrome (PRES) post-exposure to COVID-19, evidenced by heightened LDH levels (3,522 U/L at peak). After a precarious period of deteriorating kidney function and exacerbated hypertension, she responded positively to treatments, inclusive of IVIG, steroid therapies, and eculizumab, with a favorable 6-month follow-up showcasing stable laboratory results. The third case discusses a 3-year-old boy, without any medical history, manifesting HUS symptoms and COVID-19 infection. He exhibited increased LDH levels (peaking at 3,946 U/L) alongside elevated creatinine, marking renal impairment. He responded well to hemodialysis, IVIG, and steroid therapy, showcasing substantial recovery by the 19th day of hospitalization, which marked his discharge with a tapering steroid regimen.ConclusionThis case series underscores that MIS-C-associated TMA is a significant complication in pediatric COVID-19. Our findings illuminate the potential for treatment success but simultaneously emphasize the need for a more comprehensive understanding of the underlying pathophysiology.