bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reproductive characteristics, menopausal status, race and ethnicity, and risk of breast cancer subtypes defined by ER, PR and HER2 status: the Breast Cancer Etiology in Minorities study
Authors: John Esther M. , Koo Jocelyn , Phipps Amanda I. , Longacre Teri A. , Kurian Allison W. , Ingles Sue A. , Wu Anna H. , Hines Lisa M. 
Published: May 2024

Abstract
Background
Associations between reproductive factors and risk of breast cancer differ by subtype defined by joint estrogen receptor (ER), progesterone receptor (PR), and HER2 expression status. Racial and ethnic differences in the incidence of breast cancer subtypes suggest etiologic heterogeneity, yet data are limited because most studies have included non-Hispanic White women only.

Methods
We analyzed harmonized data for 2,794 breast cancer cases and 4,579 controls, of whom 90% self-identified as African American, Asian American or Hispanic. Questionnaire data were pooled from three population-based studies conducted in California and data on tumor characteristics were obtained from the California Cancer Registry. The study sample included 1,530 luminal A (ER-positive and/or PR-positive, HER2-negative), 442 luminal B (ER-positive and/or PR-positive, HER2-positive), 578 triple-negative (TN; ER-negative, PR-negative, HER2-negative), and 244 HER2-enriched (ER-negative, PR-negative, HER2-positive) cases. We used multivariable unconditional logistic regression models to estimate subtype-specific ORs and 95% confidence intervals associated with parity, breast-feeding, and other reproductive characteristics by menopausal status and race and ethnicity.

Results
Subtype-specific associations with reproductive factors revealed some notable differences by menopausal status and race and ethnicity. Specifically, higher parity without breast-feeding was associated with higher risk of luminal A and TN subtypes among premenopausal African American women. In contrast, among Asian American and Hispanic women, regardless of menopausal status, higher parity with a breast-feeding history was associated with lower risk of luminal A subtype. Among premenopausal women only, luminal A subtype was associated with older age at first full-term pregnancy (FTP), longer interval between menarche and first FTP, and shorter interval since last FTP, with similar OR estimates across the three racial and ethnic groups.

Conclusions
Subtype-specific associations with reproductive factors overall and by menopausal status, and race and ethnicity, showed some differences, underscoring that understanding etiologic heterogeneity in racially and ethnically diverse study samples is essential. Breast-feeding is likely the only reproductive factor that is potentially modifiable. Targeted efforts to promote and facilitate breast-feeding could help mitigate the adverse effects of higher parity among premenopausal African American women.
High-throughput functional mapping of variants in an arrhythmia gene, KCNE1, reveals novel biology
Authors: Muhammad Ayesha , Calandranis Maria E. , Li Bian , Yang Tao , Blackwell Daniel J. , Harvey M. Lorena , Smith Jeremy E. , Daniel Zerubabell A. , Chew Ashli E. , Capra John A. , Matreyek Kenneth A. , Fowler Douglas M. , Roden Dan M. , Glazer Andrew M. 
Published: May 2024

Abstract
Background
KCNE1 encodes a 129-residue cardiac potassium channel (IKs) subunit. KCNE1 variants are associated with long QT syndrome and atrial fibrillation. However, most variants have insufficient evidence of clinical consequences and thus limited clinical utility.

Methods
In this study, we leveraged the power of variant effect mapping, which couples saturation mutagenesis with high-throughput sequencing, to ascertain the function of thousands of protein-coding KCNE1 variants.

Results
We comprehensively assayed KCNE1 variant cell surface expression (2554/2709 possible single-amino-acid variants) and function (2534 variants). Our study identified 470 loss- or partial loss-of-surface expression and 574 loss- or partial loss-of-function variants. Of the 574 loss- or partial loss-of-function variants, 152 (26.5%) had reduced cell surface expression, indicating that most functionally deleterious variants affect channel gating. Nonsense variants at residues 56–104 generally had WT-like trafficking scores but decreased functional scores, indicating that the latter half of the protein is dispensable for protein trafficking but essential for channel function. 22 of the 30 KCNE1 residues (73%) highly intolerant of variation (with > 70% loss-of-function variants) were in predicted close contact with binding partners KCNQ1 or calmodulin. Our functional assay data were consistent with gold standard electrophysiological data (ρ =  − 0.64), population and patient cohorts (32/38 presumed benign or pathogenic variants with consistent scores), and computational predictors (ρ =  − 0.62). Our data provide moderate-strength evidence for the American College of Medical Genetics/Association of Molecular Pathology functional criteria for benign and pathogenic variants.

Conclusions
Comprehensive variant effect maps of KCNE1 can both provide insight into IKs channel biology and help reclassify variants of uncertain significance.
Online vs in-person musculoskeletal ultrasound course: a cohort comparison study
Authors: Lake Shirley , Brydges Ryan , Penney Chris , Wilson Diane , Sweezie Raquel , Bagovich Maria , Bong David , Barr Susan , Stroud Lynfa 
Published: May 2024

Abstract
Background
Point-of-care musculoskeletal (MSK) ultrasound (US) courses are typically held in-person. The COVID-19 pandemic guidelines forced courses to switch to online delivery. To determine this impact, we conducted an observational cohort study, comparing homework completion and image quality between an Online and a historical In-person cohort.

Methods
The In-person (n = 27) and Online (n = 24) cohorts attended two learning sessions spaced six months apart. The course content was the same, while the process of delivery differed. As homework, participants submitted US images biweekly for up to five months after each session. Expert faculty provided written feedback to all participants, and two independent reviewers rated the image quality for a subset of participants in each group who had completed at least 70% of their homework (In-person, n = 9; Online, n = 9). Participants self-reported their satisfaction through post-course evaluation.

Results
63% of In-Person and 71% of Online cohort participants submitted their homework images. We observed no differences in the mean amount of homework images submitted for In-person (M = 37.3%, SD = 42.6%) and Online cohorts (M = 48.1%, SD = 38.8%; p > 0.05, Mann-Whitney U Test). At course end, the cohorts did not differ in overall image quality (p > 0.05, Wilcoxon Signed-rank Test). All participants reported high levels of satisfaction.

Conclusions
A convenience sample of participants attending a basic MSK US course in-person and online did not differ statistically in homework completion, quality of submitted US images, or course satisfaction. We add to literature suggesting online learning remains a viable option post-pandemic.
FdeC expression regulates motility and adhesion of the avian pathogenic Escherichia coli strain IMT5155
Authors: Aleksandrowicz Adrianna , Kjærup Rikke Brødsgaard , Grzymajło Krzysztof , Martinez Fernando Garcia , Muñoz Javier , Borowska Dominika , Sives Samantha , Vervelde Lonneke , Dalgaard Tina Sørensen , Kingsley Robert A. , Kolenda Rafał 
Published: May 2024

AbstractAdaptation of avian pathogenic E. coli (APEC) to changing host environments including virulence factors expression is vital for disease progression. FdeC is an autotransporter adhesin that plays a role in uropathogenic Escherichia coli (UPEC) adhesion to epithelial cells. Expression of fdeC is known to be regulated by environmental conditions in UPEC and Shiga toxin-producing E. coli (STEC). The observation in a previous study that an APEC strain IMT5155 in which the fdeC gene was disrupted by a transposon insertion resulted in elevated adhesion to chicken intestinal cells prompted us to further explore the role of fdeC in infection. We found that the fdeC gene prevalence and FdeC variant prevalence differed between APEC and nonpathogenic E. coli genomes. Expression of the fdeC gene was induced at host body temperature, an infection relevant condition. Disruption of fdeC resulted in greater adhesion to CHIC-8E11 cells and increased motility at 42 °C compared to wild type (WT) and higher expression of multiple transporter proteins that increased inorganic ion export. Increased motility may be related to increased inorganic ion export since this resulted in downregulation of YbjN, a protein known to supress motility. Inactivation of fdeC in APEC strain IMT5155 resulted in a weaker immune response in chickens compared to WT in experimental infections. Our findings suggest that FdeC is upregulated in the host and contributes to interactions with the host by down-modulating motility during colonization. A thorough understanding of the regulation and function of FdeC could provide novel insights into E. coli pathogenesis.
Utilization of early supported discharge and outpatient rehabilitation services following inpatient stroke rehabilitation
Authors: Razavilar Negar , Tran Dat T. , Dukelow Sean P. , Round Jeff 
Published: May 2024

Abstract
Background
Studies examining factors associated with patient referral to early supported discharge (ESD)/outpatient rehabilitation (OPR) programs and utilization of ESD/OPR services after discharge from inpatient stroke rehabilitation (IPR) are scarce. Accordingly, we examined utilization of ESD/OPR services following discharge from IPR and patient factors associated with service utilization.

Methods
Stroke patients discharged from IPR facilities in Alberta between April 2014 and March 2016 were included and followed for one year for ESD/OPR service utilization. Multivariable linear and negative binomial regressions were used to examine association of patients’ factors with ESD/OPR use.

Results
We included 752 patients (34.4% of 2,187 patients discharged from IPR) who had 40,772 ESD/OPR visits during one year of follow-up in the analysis. Mean and median ESD/OPR visits were 54.2 and 36 visits, respectively. Unadjusted ESD/OPR visits were lower in females and patients aged ≥ 60 years but were similar between urban and rural areas. After adjustment for patient factors, patients in urban areas and discharged home after IPR were associated with 83.5% and 61.9%, respectively, increase in ESD/OPR visits, while having a right-body stroke was associated with 23.5% increase. Older patients used ESD/OPR less than their younger counterparts (1.4% decrease per one year of older age). Available factors explained 12.3% of variation in ESD/OPR use.

Conclusion
ESD/OPR utilization after IPR in Alberta was low and varied across age and geographic locations. Factors associated with use of ESD/OPR were identified but they could not fully explain variation of ESD/OPR use.
Alpha-synuclein aggregates are phosphatase resistant
Authors: Choi S. G. , Tittle T. , Garcia-Prada D. , Kordower J. H. , Melki R. , Killinger B. A. 
Published: May 2024

AbstractAlpha-synuclein (αsyn) is an intrinsically disordered protein that aggregates in the brain in several neurodegenerative diseases collectively called synucleinopathies. Phosphorylation of αsyn at serine 129 (PSER129) was considered rare in the healthy human brain but is enriched in pathological αsyn aggregates and is used as a specific marker for disease inclusions. However, recent observations challenge this assumption by demonstrating that PSER129 results from neuronal activity and can be readily detected in the non-diseased mammalian brain. Here, we investigated experimental conditions under which two distinct PSER129 pools, namely endogenous-PSER129 and aggregated-PSER129, could be detected and differentiated in the mammalian brain. Results showed that in the wild-type (WT) mouse brain, perfusion fixation conditions greatly influenced the detection of endogenous-PSER129, with endogenous-PSER129 being nearly undetectable after delayed perfusion fixation (30-min and 1-h postmortem interval). Exposure to anesthetics (e.g., Ketamine or xylazine) before perfusion did not significantly influence endogenous-PSER129 detection or levels. In situ, non-specific phosphatase calf alkaline phosphatase (CIAP) selectively dephosphorylated endogenous-PSER129 while αsyn preformed fibril (PFF)-seeded aggregates and genuine disease aggregates (Lewy pathology and Papp–Lantos bodies in Parkinson’s disease and multiple systems atrophy brain, respectively) were resistant to CIAP-mediated dephosphorylation. The phosphatase resistance of aggregates was abolished by sample denaturation, and CIAP-resistant PSER129 was closely associated with proteinase K (PK)-resistant αsyn (i.e., a marker of aggregation). CIAP pretreatment allowed for highly specific detection of seeded αsyn aggregates in a mouse model that accumulates non-aggregated-PSER129. We conclude that αsyn aggregates are impervious to phosphatases, and CIAP pretreatment increases detection specificity for aggregated-PSER129, particularly in well-preserved biological samples (e.g., perfusion fixed or flash-frozen mammalian tissues) where there is a high probability of interference from endogenous-PSER129. Our findings have important implications for the mechanism of PSER129-accumulation in the synucleinopathy brain and provide a simple experimental method to differentiate endogenous-from aggregated PSER129.
Current knowledge about stackable guides: a scoping review
Authors: Lan Romain , Marteau Camille , Mense Chloë , Silvestri Frédéric 
Published: May 2024

Abstract
Purpose
The rise of stereolithographic surgical guides and digital workflow, combined with a better knowledge of materials and loading principle, has enabled the placement of the temporary prosthesis at the time of implant placement. This scoping review aimed to assess the current knowledge available on stackable guides.

Methods
The review focused on fully edentulous or requiring total edentulism patients. The procedure studied was the use of stackable guides for edentulous patients in order to place immediate temporary prostheses. The clinical endpoint was immediate placement of the provisional prosthesis after surgery combined with a prior bone reduction using a stackable guide.

Results
12 case reports or case series articles met inclusion criteria, which did not allow an analysis by a systematic review. The included studies were case reports or case series. Most of the articles showed a base stabilized by 3 or 4 bone-pins, anchored in buccal or lingual part. Regarding the accuracy of bone reduction (ranged from 0.0248 mm to 1.98 mm) and implant placement when compared to planned, only 4 articles reported quantitative data. 11 articles showed an immediate loading with the transitional prosthesis after implant placement.

Conclusions
There are as yet no prospective or comparative studies on the efficiency of this technique. In a reliable way, stackable guides seem to be able to guide the practitioner from the flap elevation to the placement of the temporary screw-retained implant supported prosthesis. Given the lack of studies in this specific field of guided surgery, further studies are needed to confirm the clinical relevance of this technique.

Graphical Abstract
Effect of melatonin on insomnia and daytime sleepiness, in patients with obstructive sleep apnea and insomnia (COMISA): A randomized double-blinded placebo-controlled trial
Authors: Motlaq Tahereh Madani , Rahimi Besharat , Amini Shahideh 
Published: May 2024

Abstract
Background
COMISA is a common disorder that results in nighttime awakenings ,daytime sleepiness and PAP intolerance. Cognitive behavioral therapy for insomnia is used to improve PAP adherence and no medication has been evaluated in such population yet. Melatonin with its chronobiotic and antioxidant effects may have potential benefits on COMISA consequences at the appropriate dose and time. This study aimed to evaluate the effect of melatonin on sleep quality, daytime sleepiness and PAP Compliance in patients with COMISA.

Methods
This double-blind placebo trial randomly assigned eligible OSA patients who suffered from insomnia despite using PAP for over a month to receive either melatonin 10 mg or placebo. The primary outcomes were measured by changes in the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), and Functional Outcomes of Sleep Questionnaire (FOSQ-10) over one month. Adherence to PAP was measured by the results of the PAP device reports on the average length of time and number of nights that the device was used.

Results
Thirty patients were enrolled in the study after randomization. The melatonin arm showed significant improvement in all four primary outcomes compared to the placebo arm. The PSQI score was 3.836±1.839 in the melatonin arm versus 10.522±3.626 in the placebo arm (Pvalue<0.001). The ISI score was 8.476±3.568 in the melatonin arm versus 14.47±4.50 in the placebo arm (Pvalue<0.001). The ESS score was 6.854±4.334 in the melatonin arm versus 13.298±5.119 in the placebo arm (Pvalue<0.001). The FOSQ-10 score was 24.93±5.02 in the melatonin arm versus 19.87±4.24 in the placebo arm (Pvalue= 0.006). Additionally, nighttime consequences such as sleep latency and awakenings showed significant improvement in the melatonin arm. PAP devices results revealed improvement in duration of PAP use overnight.

Conclusions
Administering melatonin has been shown to improve self-reported sleep quality and PAP adherence in patients with COMISA.

Trial registration
Registration number IRCT20220105053635N1 was issued by the Iranian Registry of Clinical Trials (IRCT).
Stage IV renal cell carcinoma achieves pathologic complete response after two ipilimumab plus nivolumab courses despite severe immune-related adverse events: a case report
Authors: Takada Ryo , Fujiwara Miki , Maki Masatoshi , Nomura Naoyuki , Kono Shintaro , Fujita Akira , Masumoto Hiroshi , Takahashi Yoko , Hasegawa Yasuhisa , Tamura Koji 
Published: May 2024

Abstract
Background
Ipilimumab (Ipi) plus nivolumab (Nivo) is the recommended first-line treatment for renal cell carcinoma (RCC). This report describes a case where pancreatic metastases disappeared after only two courses of Ipi + Nivo therapy. The primary tumor was cured by surgery, and a pathological Complete Response (pCR) was observed despite multiple serious immune-related Adverse Events (irAEs).

Case presentation
A 54-year-old woman with RCC and pancreatic metastasis at stage IV, diagnosed with intermediate risk according to the International Metastatic RCC Database Consortium classification, underwent initiation of Ipi + Nivo therapy. On day 26, she developed hyperthyroidism accompanied by tachycardia, leading to the commencement of metoprolol tartrate treatment. Following the resolution of tachycardia, a second course of Ipi + Nivo therapy was administered on day 50. By day 70, the patient exhibited Grade 3 hepatic dysfunction, followed by the onset of hypothyroidism on day 75, necessitating treatment with steroids and levothyroxine. After positive treatment, a Grade 3 skin disorder emerged on day 87 while tapering steroids, prompting treatment with methylprednisolone (mPSL) pulse therapy. The skin disorder responded to steroids, allowing for tapering. However, on day 113, a recurrence of Grade 3 skin disorder occurred, necessitating another mPSL pulse. The patient responded well to treatment, exhibiting improvement in her condition. On day 131, she presented at the hospital with complaints of respiratory distress, prompting a Computed Tomography (CT) scan that revealed interstitial pneumonia. By day 272, subsequent CT imaging showed the disappearance of pancreatic metastasis and shrinkage of the primary tumor. On day 294, she underwent a laparoscopic left nephrectomy. Pathological analysis confirmed a pCR in the primary tumor, indicating successful eradication of RCC through surgical intervention.

Conclusions
This case report presents a scenario where multiple severe irAEs appeared in a patient, yet metastases disappeared after only two courses of Ipi + Nivo therapy. The patient was ultimately cured by surgery and achieved a pCR. This case highlights that despite the occurrence of severe irAEs during RCC treatment with Ipi + Nivo therapy, they can be managed appropriately to maximize the therapeutic effects of checkpoint inhibitors.
Patient interpretations of patient-reported outcome measures to assess bowel urgency: qualitative interviews in ulcerative colitis
Authors: Jairath Vipul , Gibble Theresa Hunter , Moses Richard , Klooster Brittany , Litcher-Kelly Leighann , Walker Marisa , Bernstein Madison C , Rupinski Kaelyn , McLafferty Megan , Travis Simon , Dubinsky Marla 
Published: May 2024

Abstract
Objectives
Bowel urgency is an impactful core symptom of ulcerative colitis (UC). Patient-reported outcome (PRO) questionnaires have been developed and used to assess the patient experience of this important symptom. The objective of this paper is to present evidence from qualitative research conducted to support the use and interpretation of select PRO questionnaires to assess bowel urgency related to the UC patient experience.

Methods
Qualitative interviews were conducted with ten adults with a clinician-confirmed diagnosis of moderately to severely active UC. Interviews aimed to document patient interpretation of modified recall periods for the Urgency Numeric Rating Scale (Urgency NRS), two global assessments (i.e., the Patient Global Impression of Severity [PGIS] and Patient Global Impression of Change [PGIC]), and four items (Items 11, 16, 23, and 26) of the Inflammatory Bowel Disease Questionnaire (IBDQ), and explore the patient perspective of meaningful change on these questionnaires.

Results
Both modified Urgency NRS versions (with 7-day or 3-day recall period) were interpreted as intended by most patients (≥ 88.9%), and slightly more than half of patients (60.0%) reported that the 7-day recall period was more relevant to their bowel urgency experience. Patients reported thinking of bowel urgency (≥ 80.0%) or bowel urgency-related accidents (70.0% of patients) when interpreting the global assessments and IBDQ items. Most patients reported a 1- to 3-point change as the smallest meaningful improvement that would be meaningful on the Urgency NRS (similar to findings on other questionnaires).

Conclusion
Adults with UC can understand and respond to the Urgency NRS with modified recall periods (i.e., 7-day or 3-day), interpret the conceptual content of the PGIS, PGIC, and select IBDQ items to be inclusive of bowel urgency and bowel urgency-related accidents, and select answers representing meaningful improvements on the Urgency NRS, PGIS, PGIC, and IBDQ item response scales. These results further contribute patient-centered data to existing UC and bowel urgency research.