bluuebunny/crossref_metadata_2025_split huggingface dataset:
Change in the Perception of Oral Antibiotics Among Medical Students After Participating in a Parenteral-to-Oral Conversion Program for Highly Bioavailable Antibiotics
Authors: Jang Wooyoung , Pai Hyunjoo , Kim Bongyoung 
Published: October 2022

Abstract

Background
Appropriate conversion of antibiotics from a parenteral to the oral route can lower the risk of catheter-associated infections, reduce medical costs, and shorten hospitalization. This study investigated the effect of a parenteral-to-oral conversion program for highly bioavailable antibiotics on the perceptions of medical students regarding oral antibiotics.

Methods
In 2021, the parenteral-to-oral conversion program was implemented as one of the activities of an antimicrobial stewardship program at a tertiary-care hospital in South Korea. This program was also implemented for fifth-year medical students in the hospital's infectious diseases department as a core clinical practice course. Medical students reviewed the medical records of patients taking antibiotics with a high oral bioavailability and wrote a recommendation for oral conversion after confirmation by an infectious disease specialist. A survey on the perception of oral antibiotics was administered to medical students before and after clinical practice to evaluate the educational effect of the program.

Results
A total of 923 cases were reviewed, and more than one-fifth of the antibiotics with a high oral bioavailability were administered parenterally despite their oral conversion (20.6%, 190/923). Of these, 24.2% (46/190) accepted the written proposal within 48 hours, and 43.7% (83/190) declined the proposal. Through this program, students gained a proper perception of oral antibiotics.

Conclusions
The parenteral-to-oral conversion program demonstrated an acceptance rate of oral antibiotic conversion in the hospital of 24.2% and had significant educational benefits for medical students, giving them the ability to construct an appropriate perception of oral antibiotics.
Demystifying Legal Personhood for Non-Human Entities: A Kelsenian Approach
Authors: Buocz Thomas , Eisenberger Iris 
Published: October 2022

Abstract
This article aims to show that minimalist theories of legal personhood are particularly well suited to evaluating legal personhood proposals for non-humans. It adopts the perspective of Hans Kelsen’s theory of legal personhood, which reduces legal persons to bundles of legal norms. Through the lens of Kelsen’s theory, the article discusses two case studies: legal personhood for natural features in New Zealand and legal personhood for robots in the EU. While the New Zealand case was an acclaimed success, the EU’s proposal was heavily criticised and eventually abandoned. The article explains these widely differing outcomes by highlighting the relevant legal norms and their addressees rather than legal personhood itself. It does so by specifying the rights and obligations that constitute the legal persons, by preventing the attribution of any other rights and obligations to these persons and, finally, by tracing who is ultimately addressed by the relevant rights and obligations.
Characterization of the Functions of Starch Synthase IIIb Expressed in the Vegetative Organs of Rice (Oryza sativa L.)
Authors: Morita Ryutaro , Crofts Naoko , Miura Satoko , Ikeda Ken-ichi , Aoki Naohiro , Fukayama Hiroshi , Fujita Naoko 
Published: October 2022

Abstract
Rice is the model C3 crop for investigating the starch biosynthesis mechanism in endosperm because of its importance in grain production. However, little is known about starch biosynthesis in the vegetative organs of rice. In this study, we used novel rice mutants by inserting Tos17 into the starch synthase (SS) IIIb gene, which is mainly expressed in the leaf sheath (LS) and leaf blade (LB), and an ss1 mutant to clarify the differences in roles among SS isozymes during starch biosynthesis. Native polyacrylamide gel electrophoresis (PAGE)/activity staining for SS, using LS and LB of ss mutants, revealed that the lowest migrating SS activity bands on the gel were derived from SSIIIb activity and those of two ss3b mutants were not detected. The apparent amylose content of LS starch of ss3b mutants increased. Moreover, the chain-length distribution and size-exclusion chromatography analysis using ss mutants showed that SSIIIb and SSI synthesize the B2–B3 chain and A–B1 chain of amylopectin in the LS and LB respectively. Interestingly, we also found that starch contents were decreased in the LS and LB of ss3b mutants, although SSI deficiency did not affect the starch levels. All these results indicated that SSIIIb synthesizes the long chain of amylopectin in the LS and LB similar to SSIIIa in the endosperm, while SSI synthesizes the short chain in the vegetative organ as the same in the endosperm.
Autoimmune activation and hypersensitization of the AT1 and ETA receptors contributes to vascular injury in scleroderma renal crisis
Authors: Hegner Björn , Kretzschmar Tobias , Zhu Nan , Kleinau Gunnar , Zhao Hongfan , Kamhieh-Milz Julian , Hilger Julia , Schindler Ralf , Scheerer Patrick , Riemekasten Gabriela , Philippe Aurélie , Catar Rusan 
Published: October 2022

Abstract

Objectives
Scleroderma renal crisis (SRC) is a rare vascular complication of systemic sclerosis with substantial risks for end-stage renal disease and premature death. Activating autoantibodies (Abs) targeting the angiotensin II type 1 (AT1R) and the endothelin-1 type A receptor (ETAR) have been identified as predictors for SRC. Here, we sought to determine their pathogenic significance for acute renal vascular injury potentially triggering kidney failure and malignant hypertension.

Methods
IgG from patients with SRC was studied for AT1R and ETAR dependent biologic effects on isolated rat renal interlobar arteries and vascular cells including contraction, signalling and mechanisms of receptor activation.

Results
In myography experiments, patient IgG exerted vasoconstriction sensitive to inhibition of AT1R and ETAR. This relied on MEK-ERK signalling indicating functional relevance of anti-AT1R and anti-ETAR Abs. The contractile response to angiotensin II and endothelin-1 was amplified by patient IgG containing anti-AT1R and anti-ETAR Abs with substantial crosstalk between both receptors implicating autoimmune receptor hypersensitization. Co-immunoprecipitation experiments indicated heterodimerization between both receptor types which may enable the observed functional interrelation by direct structural interactions.

Conclusion
We provide experimental evidence that agonistic Abs may contribute to SRC. This effect is presumably related to direct receptor stimulation and additional allosteric effects, at least in heterodimeric receptor constellations. Novel therapies targeted at autoimmune hyperactivation of AT1R and ETAR might improve outcomes in severe cases of SRC.
Predicting human cardiac QT alterations and pro-arrhythmic effects of compounds with a 3D beating heart-on-chip platform
Authors: Visone Roberta , Lozano-Juan Ferran , Marzorati Simona , Rivolta Massimo Walter , Pesenti Enrico , Redaelli Alberto , Sassi Roberto , Rasponi Marco , Occhetta Paola 
Published: October 2022

Abstract
Determining the potential cardiotoxicity and pro-arrhythmic effects of drug candidates remains one of the most relevant issues in the drug development pipeline (DDP). New methods enabling to perform more representative preclinical in vitro studies by exploiting induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) are under investigation to increase the translational power of the outcomes. Here we present a pharmacological campaign conducted to evaluate the drug-induced QT alterations and arrhythmic events on uHeart, a 3D miniaturized in vitro model of human myocardium encompassing iPSC-CM and dermal fibroblasts embedded in fibrin. uHeart was mechanically trained resulting in synchronously beating cardiac microtissues in 1 week, characterized by a clear field potential (FP) signal that was recorded by means of an integrated electrical system. A drug screening protocol compliant with the new International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines was established and uHeart was employed for testing the effect of 11 compounds acting on single or multiple cardiac ion channels and well-known to elicit QT prolongation or arrhythmic events in clinics. The alterations of uHeart’s electrophysiological parameters such as the beating period, the FP duration, the FP amplitude, and the detection of arrhythmic events prior and after drug administration at incremental doses were effectively analyzed through a custom-developed algorithm. Results demonstrated the ability of uHeart to successfully anticipate clinical outcome and to predict the QT prolongation with a sensitivity of 83.3%, a specificity of 100% and an accuracy of 91.6%. Cardiotoxic concentrations of drugs were notably detected in the range of the clinical highest blood drug concentration (Cmax), qualifying uHeart as a fit-to-purpose preclinical tool for cardiotoxicity studies.
Blunt chest wall trauma
Authors: Beloy Victoria , Dull Matthew 
Published: October 2022

ABSTRACT
Blunt injuries to the chest wall, specifically those related to rib fractures, need to be promptly identified and effectively managed to reduce patient morbidity and mortality. Furthermore, judicious use of multimodal pain management and early identification of patients who will benefit from the surgical stabilization of rib fractures are paramount to optimal outcomes.
Single Site Experience of the use of Monoclonal Antibodies for the Treatment of COVID-19 in High-risk Pediatric and Young Adult Patients
Authors: Bahakel Hannah , Murphy Catherine , Frenck Robert W. , Grimley Michael S. , Marsh Rebecca A. , Paulsen Grant C. , Haslam David B. , Phillips Christine L. , Courter Joshua , Spearman Paul , Schulert Grant , Danziger-Isakov Lara 
Published: October 2022

Background:
Effective therapeutic agents for the treatment of COVID-19 have been investigated since the onset of the pandemic. Monoclonal antibodies targeting the spike protein of SARS-CoV-2 have been developed for the treatment of mild or moderate COVID disease in high-risk populations. Despite widespread use in the adult population, data are limited on the safety and efficacy of monoclonal antibody infusions in the adolescent and young adult population.

Methods:
Patients who received bamlanivimab, bamlanivimab-etesevimab, casirivimab-imdevimab, or sotrovimab for treatment of mild-to-moderate COVID-19 disease at Cincinnati Children’s Hospital Medical Center from 5/1/2020 to 3/1/2022 were identified retrospectively. Patient data including demographics, adverse events, and outcomes were extracted from patients’ charts and summarized by standard descriptive summaries.

Results:
Ninety-four patients received monoclonal antibody therapy, of which 14 (14.9%) received either bamlanivimab or bamlanivimab-etesevimab, 54 (57.4%) received casirivimab-imdevimab, and 26 (27.6%) received sotrovimab. Ten patients (10.6%) experienced one or more infusion-related adverse event. Of the patients who experienced adverse events, all resolved with cessation of infusion. No life-threatening events or deaths occurred. Within 90 days of receiving a monoclonal antibody, 12 patients (12.7%) required additional medical care for ongoing COVID symptoms. Five of these were either hospitalized or received escalation of care while already in the hospital. All subsequently fully recovered. Neither infusion-related adverse events nor progression to hospitalization for ongoing COVID-19 symptoms following monoclonal antibody administration were associated with any particular underlying condition.

Conclusions:
Overall, monoclonal antibodies are reasonably well-tolerated COVID-19 therapies in high-risk adolescent and young adult populations.
Preconception health optimization in women with polycystic ovary syndrome − how to find the time?
Authors: Lennon Clare , Voss Kathryn , Vitek Wendy S. 
Published: October 2022

Purpose of review
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women, the most common cause of infertility among women and a major contributor to pregnancy complications.

Recent findings
Diagnostic and associated features of PCOS, including hyperandrogenism, insulin resistance, and obesity, contribute to the 2−4-fold increased risk of pregnancy-induced hypertension and preeclampsia, gestational diabetes and preterm birth observed among pregnant women with PCOS. PCOS should be diagnosed according to the 2018 International Guideline. Screening for and optimizing management of hypertension, impaired glucose tolerance and obesity in the preconception window in women with PCOS provides an opportunity to increase the odds of a spontaneous pregnancy, live birth with fertility treatment and possibly reduce the risk of pregnancy complications.

Summary
Providers should prioritize individualizing recommendations for preconception health optimization in women with PCOS in order to maximize the chance of conception, a healthy pregnancy and the health of future generations.
NUT Carcinoma in Children and Adolescents: The Expert European Standard Clinical Practice Harmonized Recommendations
Authors: Lemelle Lauriane , Flaadt Tim , Fresneau Brice , Moya-Plana Antoine , Timmermann Beate , Roganovic Jelena , Ferrari Andrea , Fichera Giulia , Lauer Ulrich M. , Ben-Ami Tal , Schneider Dominik T. , Vokuhl Christian , Bolle Stephanie , Fox Elisabeth , DuBois Steven G. , Rodriguez-Galindo Carlos , Bisogno Gianni , Surun Aurore , Brecht Ines B. , Orbach Daniel 
Published: October 2022

Background and Aims:
Nuclear protein of the testis (NUT) carcinoma (NC) is a rare and highly aggressive tumor mainly occurring in adolescents and young adults, defined by the presence of a somatic NUTM1 rearrangement. The aim is to establish internationally harmonized consensus recommendations for the diagnosis and treatment of adolescents and young adults with NC in the framework of the European Reference Network for Paediatric Oncology.

Methods:
The European Cooperative Study Group for Pediatric Rare Tumors developed recommendations according to the Consensus Conference Standard Operating procedure methodology and reviewed by external “experts.” No evidence of level I to II exists. Recommendations were developed based on published prospective (level III), but more frequently retrospective series (level IV), case reports (level V), and personal expertise (level V). In addition, “strength” of recommendations were categorized by grading (grade A to E).

Results:
Histology is mandatory for the diagnosis of NC, including immunolabeling with anti-NUT antibodies and molecular biology (NUTM1 rearrangement) (level V; grade A). Treatment of NC usually combines aggressive approaches in multimodal regimens. Chemotherapy should be considered as first-line treatment (neoadjuvant vincristine-adriamycin-ifosfamide/cisplatin-adriamycin-ifsofamide or vincristine-doxorubicin-cyclophosphamide/ifosfamide-etoposide) for unresectable or metastatic tumor (ie, 3 courses), rapidly followed by local treatment (level IV; grade B). Referral to a specialized surgical oncology center is highly recommended (level V; grade A). In localized NC, a complete microscopic surgical resection should be attempted whenever and as soon as possible, followed by primary irradiation (60 to 70 Gy) and involved lymph nodes area (level IV; grade B). For head and neck tumors, a systematic neck dissection might be considered, even if N0 (level V; grade C). Adjuvant postirradiation chemotherapy is recommended, for a total of 9 to 12 courses (level IV; grade B). For first-line resected tumors, concomitant adjuvant chemotherapy to radiotherapy may be discussed (level IV; grade B). Targeted therapies and immunotherapeutic regimens should be delivered in the setting of prospective trials (level V; grade B).

Conclusions:
This project leads to a consensus strategy based on international experience with this very rare disease.
It Is Not Just the Southeast—Geographically Pervasive Racial Disparities in Neisseria gonorrhoeae Between Non-Hispanic Black and White US Women
Authors: Rowlinson Emily , Stenger Mark R. , Valentine Jo A. , Hughes James P. , Khosropour Christine M. , Golden Matthew R. 
Published: October 2022

Racial disparities in female gonorrhea rates are not confined to the Southeast; both relative and absolute disparities are equivalent or larger in areas of the Northeast, Midwest, and West.

Background
Spatial analyses of gonorrhea morbidity among women often highlight the Southeastern United States but may not provide information on geographic variation in the magnitude of racial disparities; such maps also focus on geographic space, obscuring underlying population characteristics. We created a series of visualizations depicting both county-level racial disparities in female gonorrhea diagnoses and variations in population size.

Methods
We calculated county- and region-level race-specific relative rates (RelR) and between-race rate differences (RDs) and rate ratios (RRs) comparing gonorrhea case rates in non-Hispanic Black (NHB) versus non-Hispanic White (NHW) women. We then created proportional symbol maps with color representing counties' RelR/RD/RR category and symbol size representing counties' female population.

Results
Gonorrhea rates among NHB women were highest in the Midwest (718.7/100,000) and West (504.8), rates among NHW women were highest in the West (74.1) and Southeast (72.1). The RDs were highest in the Midwest (654.6 excess cases/100,000) and West (430.7), whereas the RRs were highest in the Northeast (12.4) and Midwest (11.2). Nearly all US counties had NHB female rates ≥3× those in NHW women, with NHB women in most highly populated counties experiencing ≥9-fold difference in gonorrhea rates.

Conclusions
Racial disparities in gonorrhea were not confined to the Southeast; both relative and absolute disparities were equivalent or larger in magnitude in areas of the Northeast, Midwest, and West. Our findings help counter damaging regional stereotypes, provide evidence to refocus prevention efforts to areas of highest disparities, and suggest a useful template for monitoring racial disparities as an actionable public health metric.
Iodinated Contrast Enhancement of Breast Cancer on Prone Multidetector Computed Tomography—Preliminary Findings
Authors: Felipe Vinicius C. , Barbosa Paula N.V.P. , Chojniak Rubens , Bitencourt Almir G.V. 
Published: October 2022

Objectives
Contrast-enhanced breast imaging has gained increasing importance in the diagnosis and management of breast cancer. The aim of this study was to assess breast cancer enhancement after contrast administration on prone multidetector computed tomography (MDCT).

Materials and Methods
This retrospective, unicentric, institutional review board-approved study included patients with newly diagnosed breast cancer who were submitted to contrast-enhanced MDCT in prone position, with image acquisition before and after nonionic iodinated contrast administration.

Results
Sixty breast cancer patients aged between 31 and 74 years (mean, 49 years) were included. Most patients (n = 50, 83.3%) had no special type invasive breast carcinoma and luminal subtype (n = 45, 75%). All index breast tumors were identified on prone MDCT. Forty-three cases (70.5%) presented as mass, 13 (21.3%) as nonmass enhancement and 4 (6.6%) as both mass and nonmass enhancement. Mean tumor density was 37.8 HU and 87.9 HU on precontrast and postcontrast images, respectively. Mean contrast enhancement was 50.2 HU (range, 20–109 HU). There were no statistically significant differences in tumor enhancement according to histological type, molecular subtype, nuclear grade, tumor size, or imaging presentation.

Conclusions
Our results show that breast cancer usually can be identified and have significant contrast enhancement on prone MDCT images. This method could be used as an alternative when other contrast-enhanced breast imaging methods are not available.
Which Body Composition Parameters on Computed Tomography Are More Successful in Predicting the Prognosis of COVID-19 Patients?
Authors: Ufuk Furkan , Utebey Ayse Ruksan , Yavas Huseyin Gokhan , Baser Oncel Sevin , Akbudak Ismail Hakki , Sari Tugba 
Published: October 2022

Objectives
The aims of the study are to compare the body composition parameters (BCPs), which have been reported to have a prognostic impact, in COVID-19 patients, and to determine the most influential BCP(s) on the prognosis.

Methods
Unenhanced chest computed tomography examinations of COVID-19 cases were assessed regarding the severity of pneumonia, pectoralis muscle area and density (PMA, PMD), visceral adipose tissue area (VAA), waist circumference, waist to paravertebral muscle circumference ratio, coronary artery calcification severity, and paravertebral muscle area at the T5 vertebral level. A second observer repeated measurements and an intraclass correlation coefficient score were used for interobserver agreement. The relationship between data and patient outcomes (intubation, death) was investigated using multivariable logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of BCPs in predicting outcomes.

Results
A total of 238 (121 males, median age, 48 years [interquartile range, 36–63 years]) consecutive COVID-19 patients with chest computed tomography were investigated. Twenty-four patients (10.08%) were intubated, and 15 patients (6.3%) died during at least 1 month of follow-up. Waist to paravertebral muscle circumference ratio, PMA, PMD, and T5 vertebral level were significantly associated with intubation in the multivariable analysis. Pectoralis muscle density and PMA were significantly associated with death. Pectoralis muscle density showed the highest AUC for the prediction of intubation and death (AUC of 0.814 and 0.871, respectively). There was a good to excellent agreement between observers (intraclass correlation coefficient range, 0.899–0.998).

Conclusions
Pectoralis muscle density is the most influential BCP in predicting intubation and death in COVID-19 patients.
Optimizing Flap Harvest in Auricular Reconstruction
Authors: Fernando Shanik J. , Davis Seth J. , Dedhia Raj D. , Sowder Justin C. , Ramachandra Tara , Stephan Scott J. 
Published: October 2022

Introduction:
The temporoparietal fascial (TPF) and occipital cranial fascial (OCP) flaps are the mainstay of implant coverage in alloplastic auricular reconstruction. Their optimal design is critical for elevating a robust flap that ultimately leads to favorable outcomes.

Materials and Methods:
Sixteen TPF and OCP dissections were performed on 8 cadaveric specimens. Vascular anatomy and key landmarks were documented. The minimum flap size that incorporated ideal vasculature and would appropriately cover a porous polyethylene implant was measured.

Results:
The minimum flap dimensions (length × width × base width) to cover a standard PPE auricular implants were on average 11×8.3×6.4 cm for TPF and 13.1×8.6×6.5 cm for OCP. The average axial length of the superficial temporal artery and occipital artery were 12.51 and 13.2 cm, respectively. An “occipital elbow” was located on average 8.2 cm posterior to the external acoustic canal. The postauricular fascia contained additional contributions from the occipital artery and mastoid emissary vein, which was located on average 5.9 cm posterior to the superficial temporal artery.

Conclusions:
This study highlights the anatomic features behind optimal TPF and OCP flap design for auricular reconstruction. Contributions to axial length and anatomic relationships of their primary arterial supply, significance of the occipital elbow as a reliable landmark for fascial dissection, and importance of the postauricular fascia and its vascular supply for flap viability are emphasized. Ultimately, the authors provide minimal dimensions for both TPF and OCP flaps to obtain adequate alloplastic implant coverage.