bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling of PTF1‐J and PTF1‐L Heterotrimeric Transcription Factor Complexes (LB87)
Authors: Pedigo KK , Mainali Rabina , Glispin Christopher , Noble Gabe , Petters Garrett , Allmam Casey , Agua Alec Agua , Bauzaldua Adrian , Crane Ben , Aranoff Max , Gonzales Nicholas , Park Christine , Chung Elizabeth , Montoux Amy , Flabiano Meredith , Espinosa Anika , Almazan Selena , Kaye Cassidy , Crowling Anna , Chandler Chandria , Allman Julianna , Coats Ward , MacDonald Raymond 
Published: June 2021

Students in Biomedical Research Studies at Hillcrest High School in Dallas, Texas participate in an ongoing research program at the University of Texas Southwestern Medical Center to study the structure and function of a transcription factor complex. Ptf1a is a transcription factor that is crucial to the development of the embryonic pancreas. Its functional form is in a trimeric complex composed of a heterodimer of E12/E47 and Ptf1a (basic helix‐loop‐helix transcription factors), and either Rbpj or Rbpjl (paralogs, also present in Notch signaling). The Rbpj form of the complex (PTF1‐J) is required for the early stage of pancreatic development. Subsequently, the Rbpjl‐form (PTF1‐L) is required for the formation of mature acinar cells of the exocrine pancreas. The Hillcrest SMART (Students Modeling A Research Topic) Team using 3D printing technology has generated models for the PTF1‐J and PTF1‐L transcription factor complexes. The models provide the orientation of the Ptf1a/E12 heterodimer relative to the Rbpj and Rbpjl proteins and characterizes interactions formed between Ptf1a (tryptophan 298) and a hydrophobic pocket present in the b‐trefoil domain of Rbpj or Rbpjl. Determination of the structures for the PTF1‐J and PTF1‐L complexes will help elucidate the structural determinants and the mechanism for the strong cooperative DNA binding of these complexes.Grant Funding Source: Supported by a grant from NIH‐SEPA and NIH‐CTSA.
Discordance Between Respiratory Drive and Sedation Depth in Critically Ill Patients Receiving Mechanical Ventilation*
Authors: Dzierba Amy L. , Khalil Anas M. , Derry Katrina L. , Madahar Purnema , Beitler Jeremy R. 
Published: June 2021

OBJECTIVES:
In mechanically ventilated patients, deep sedation is often assumed to induce “respirolysis,” that is, lyse spontaneous respiratory effort, whereas light sedation is often assumed to preserve spontaneous effort. This study was conducted to determine validity of these common assumptions, evaluating the association of respiratory drive with sedation depth and ventilator-free days in acute respiratory failure.

DESIGN:
Prospective cohort study.

SETTING:
Patients were enrolled during 2 month-long periods in 2016–2017 from five ICUs representing medical, surgical, and cardiac specialties at a U.S. academic hospital.

Patients:
Eligible patients were critically ill adults receiving invasive ventilation initiated no more than 36 hours before enrollment. Patients with neuromuscular disease compromising respiratory function or expiratory flow limitation were excluded.

INTERVENTIONS:
Respiratory drive was measured via P0.1, the change in airway pressure during a 0.1-second airway occlusion at initiation of patient inspiratory effort, every 12 ± 3 hours for 3 days. Sedation depth was evaluated via the Richmond Agitation-Sedation Scale. Analyses evaluated the association of P0.1 with Richmond Agitation-Sedation Scale (primary outcome) and ventilator-free days.

MEASUREMENTS AND MAIN RESULTS:
Fifty-six patients undergoing 197 bedside evaluations across five ICUs were included. P0.1 ranged between 0 and 13.3 cm H2O (median [interquartile range], 0.1 cm H2O [0.0–1.3 cm H2O]). P0.1 was not significantly correlated with the Richmond Agitation-Sedation Scale (R
Spearman, 0.02; 95% CI, –0.12 to 0.16; p = 0.80). Considering P0.1 terciles (range less than 0.2, 0.2–1.0, and greater than 1.0 cm H2O), patients in the middle tercile had significantly more ventilator-free days than the lowest tercile (incidence rate ratio, 0.78; 95% CI, 0.65–0.93; p < 0.01) or highest tercile (incidence rate ratio, 0.58; 95% CI, 0.48–0.70; p < 0.01).

CONCLUSIONS:
Sedation depth is not a reliable marker of respiratory drive during critical illness. Respiratory drive can be low, moderate, or high across the range of routinely targeted sedation depth.
Loop colostomy to relieve debilitating chronic constipation in spina bifida patients: a case report
Authors: Kale Supriya V. , Chaudhry Arooj F. , Wazir Hersh , Yansen Michael , Tiesenga Frederick 
Published: June 2021

Introduction and importance:
Spina bifida often results in neurogenic bowel dysfunction due to the loss of sensory and motor control of the gastrointestinal tract. This dysfunction further leads to the difficulty of emptying the bowel, resulting in constipation. Therefore, a complication of spina bifida is chronic constipation. Long-standing constipation greatly affects the quality of life. Chronic constipation leads to loss of social and work opportunities, causes severe discomfort, and increases the potential for several secondary complications such as hemorrhoids, anal fissures, and urinary incontinence. Several treatment measures can be considered to relieve chronic constipation in order to improve the quality of life of patients with spina bifida.

Case presentation:
The purpose of this report is to present a rare case of an adult patient with spina bifida who underwent a loop colostomy procedure as a treatment option for her debilitating chronic constipation symptoms. The patient’s chronic constipation and associated symptoms led to an immense decrease in quality of life. After several failed attempts at relieving constipation, a loop colostomy procedure was conducted.

Clinical discussion:
A loop colostomy is a surgical procedure leading to exteriorization of the colon. As seen in this case, a loop colostomy can be considered as a curative option for chronic constipation specifically in patients with spina bifida. The surgical procedure alleviated chronic constipation and its associated symptoms.

Conclusion:
Chronic constipation and associated symptoms in adult patients with spina bifida can be treated with a loop colostomy procedure. This procedure is an innovative and helpful option for these specific patients. The possibility of increased quality of life in patients with impairing symptoms makes the loop colostomy procedure an optimistic treatment option.
Prognostic value of masked uncontrolled apparent resistant hypertension detected through home blood pressure monitoring
Authors: Barochiner Jessica , Aparicio Lucas S. , Martínez Rocío , Alfie José , Marín Marcos J. 
Published: June 2021

Objective:
Resistant hypertension carries a poor prognosis and current guidelines recommend the exclusion of the white-coat phenomenon for proper diagnosis. However, guidelines do not focus on patients treated with at least three drugs whose blood pressure (BP) is controlled at the office but elevated out of it. We aimed at determining whether this masked uncontrolled apparent resistant hypertension (MUCRH) detected through home blood pressure monitoring (HBPM) has prognostic value for fatal and nonfatal events in these hypertensive patients.

Methods:
Hypertensive patients treated with at least three drugs who performed a baseline HBPM between 2008 and 2015 were followed to register the occurrence of total mortality, cardiovascular mortality, and fatal and nonfatal cardiac and cerebrovascular events. MUCRH was defined as office blood pressure less than 140/90 mmHg and home BP at least 135 and/or 85 mmHg. Multivariable Cox proportional hazard models were adjusted to determine the independent prognostic value of MUCRH for the events of interest.

Results:
We included 470 patients, 35.5% male, mean age 71.9 years, and treated with 3.3 antihypertensive drugs on average. Among study population, 15.5% had MUCRH (33.3% when considering only patients with adequate BP control at the office). Median follow-up was 6.7 years. In multivariable models, MUCRH was an independent predictor for cardiovascular mortality and cerebrovascular events: hazard ratio 4.9 (95% CI 1.2–19.9, P = 0.03) and 5.1 (95% CI 1.5–16.9, P = 0.01), respectively.

Conclusion:
MUCRH is not rare and is independently associated with cardiovascular morbidity and mortality. The systematic monitoring of intensively treated individuals through HBPM would be useful for the detection of patients at increased risk of events.
Efficacy, Safety, and Retreatment Benefit of Micropulse Transscleral Cyclophotocoagulation in Glaucoma
Authors: Chamard Chloé , Bachouchi Alex , Daien Vincent , Villain Max 
Published: June 2021

Precis:
Micropulse transscleral cyclophotocoagulation (MP-TSCPC) with a 120-second setting reduces intraocular pressure (IOP) with a 6-month success of 45.5%. Only late (>6 mo) failure seem to present a benefit for retreatment.

Purpose:
The purpose of this study was to assess MP-TSCPC efficacy, safety, factors of success, and retreatment benefit in open-angle glaucoma.

Patients and Methods:
A retrospective consecutive case series study. We included patients with open-angle glaucoma who were naive of a cycloablative procedure and underwent MP-TSCPC at 2000 mW for 120 seconds between May 1, 2017, and October 31, 2019. Success was defined as IOP >5 and ≤21 mm Hg with IOP reduction ≥20% from baseline, without any retreatment and visual acuity better than negative light perception. MP-TSCPC retreatment was early and late, before and after 6 months postoperatively, respectively.

Results:
We included 94 eyes in 94 patients [mean (SD) age: 67.2 (13.4) y; 47.9% women]. The mean preoperative IOP was 24.9 (7.1) mm Hg and was reduced to 18.9 (6.3) at month 6 (P<0.0001). The success rate decreased progressively over time and reached 45.5% at 6 months. Patients with 6-month surgical success had lower mean axial length than others [24.1 (1.5) vs. 25.5 (2.1) mm, P=0.05]. In patients with early and late MP-TSCPC retreatment, the 6-month success rate was 16.7% and 63.6%, respectively.

Conclusions:
MP-TSCPC performed with a 120-second setting reduced IOP, with 45.5% success at month 6 and few complications. Axial length was newly described as affecting success, probably linked to the ciliary-body position. Retreatment seemed to be of little benefit in nonresponders or those with early failure. Further studies on laser settings and ciliary-body location are required to find the best risk-benefit protocol.
Undergraduate teaching of urology: Quo vadis?
Authors: Pereira Diogo , Catarino Raquel , Rodrigues Vasco , Costa Gabriel , Silva João , Carmo-Reis Frederico , Martins-Silva Carlos 
Published: June 2021

Abstract

Background:
The undergraduate teaching of urology is not uniform in the various European medical schools and even absent in some of them, despite the widespread adoption of the Bologna process, which advocates a standardization and harmonization of medical education. Our aim was to evaluate the perception of junior doctors about the undergraduate teaching of Urology and the exposure to the specialty of Urology in undergraduate education in Portuguese medical schools.

Methods:
A questionnaire was emailed to all physicians who first enrolled in the Board of Portuguese Doctors in 2017 and 2018. The questionnaire consisted of several questions about specialty exposure, pathology, and basic urological procedures. A database for statistical analysis was created.

Results:
One hundred and eighty-six answers were considered valid. Although almost all participant physicians attribute considerable importance to Urology specialty, most find their exposure to urological pathology and basic urological procedures to be inappropriate in medical school. Urinary lithiasis and lower urinary tract symptoms are the subjects on which doctors feel most prepared after graduating. Interestingly, 63.4% of doctors consider that the education they had in college was preponderant in choosing their specialty.

Conclusions:
The teaching of Urology in Portuguese Medical Schools is considered by junior doctors as inadequate, not reflecting the importance of this specialty in the clinical practice. These results are like those found in other countries. A reflection and consequent change of the teaching paradigm is necessary, namely at the practical teaching level.
Readiness for Hospital Discharge and Its Correlates Among People Living With HIV in Hunan, China: A Cross-sectional Study
Authors: Zhang Xiaoxia , Tang Chulei , Xiao Xueling , Sun Manman , Wang Honghong 
Published: June 2021

Abstract
We aimed to (a) describe the readiness for hospital discharge in people living with HIV and (b) explore factors associated with readiness for hospital discharge. A cross-sectional survey was conducted at two infectious disease hospitals in Hunan, China, from May to November 2017. The readiness for hospital discharge scale (RHDS) was used to assess discharge readiness. The average item mean for the RHDS ranges from 0 to 10, and higher scores represent a higher level of readiness for hospital discharge. The mean score of the RHDS was 7.78 (95% confidence interval 7.586–7.968), and 27.6% of participants (n = 56/203) felt unready for discharge (RHDS <7). We found that older age, lack of medical insurance, lower self-rated health status, poorer quality of discharge teaching, and more severe depressive symptoms were significantly associated with a lower level of readiness for hospital discharge. Interventions are needed to improve readiness of people living with HIV for hospital discharge in Hunan, China, especially for those of advanced age, without medical insurance, with worse self-rated health status, and those with higher levels of depressive symptoms.
Criminalization of Sexual and Gender Minorities and Its Consequences for the HIV Epidemic in Zambia: A Critical Review and Recommendations
Authors: Yelverton Valerie , Qiao Shan , Menon J. Anitha , Ngosa Levy , Kabwe McLean , Harrison Sayward , Weissman Sharon , Li Xiaoming , W. Harper Gary 
Published: June 2021

Abstract
To elaborate the negative impacts of sexual and gender minority (SGM)-related legislation for the HIV epidemic in Zambia, we reviewed Zambian legislation that restricts the rights of SGM people and synthesized its consequences. We retrieved legal documents through the National Assembly of Zambia and the Zambia Legal Information Institute and conducted a critical review based on four academic databases following thematic synthesis methodology. Eighteen literature records and six Zambian laws were included in the review. Existing laws criminalize same-sex sexual behavior and restrict same-sex marriage and the adoption of children. Anti-SGM legislation has limited legal protections for SGM people and increased vulnerability of criminal prosecution and HIV exposure, persistent stigma/discrimination, insufficient public health resources, and lessened access to HIV-related services. We recommend enacting legal protections for SGM people, decriminalizing anti-SGM laws, rectifying misinformation to destigmatize SGM people, targeting health care for SGM people, and including SGM people in the national HIV strategy.
Hereditary Spherocytosis as an Atypical Presentation of Anemia in Ulcerative Colitis
Authors: Cho Moo , Tucker Suzanne , Choi Lillian 
Published: June 2021

Anemia is encountered in up to two-thirds of all patients with inflammatory bowel disease (IBD). We are reporting a case of a 9-year-old female with history of very early onset IBD ulcerative colitis, and primary sclerosing cholangitis who was found to have hereditary spherocytosis as the etiology of her anemia. Despite good clinical response to IBD therapy, she continued to have persistent normocytic anemia. Liver biopsy and magnetic resonance cholangiopancreatography for uptrending liver transaminases demonstrated iron deposition which led to a T2-weighted magnetic resonance imaging study that quantified significant iron deposition in her liver and kidneys. Without any history of blood transfusions, these findings were concerning for hereditary hemochromatosis, but the hereditary hemochromatosis gene test was negative. Whole genome sequencing identified a pathogenic de novo variant consistent with hereditary spherocytosis.

Table of Contents Summary:
A novel presentation of anemia in inflammatory bowel disease
18F-Choline PET/CT, MRI, and Software-Based Image Fusion Analysis in Patients With Primary Hyperparathyroidism
Authors: Hofer Thomas , Kronbichler Juergen , Huber Helmut , Hergan Benedikt , Kaiser Bernhard , Shamiyeh Andreas , Fellner Franz , Gabriel Michael 
Published: June 2021

Purpose
The aim of this study was to evaluate the diagnostic performance of 18F-choline PET and MRI in patients with primary hyperparathyroidism. Furthermore, the additional value of software-based PET/MRI scan fusion was analyzed.

Patients and Methods
This retrospective study includes 42 patients (38 women) with an age between 32.5 and 79.1 years. PET/CT scans were performed on a dedicated system after injection of 250 to 350 MBq 18F-choline. For the MRI examination, T1-weighted images of the cervical region were used. The image fusion was made by anatomical coregistration using an automated algorithm based on mutual information.

Results
A total of 46 lesions were discovered and histologically confirmed in 42 patients. Histopathological examination revealed 38 adenomas and 8 hyperplasias. This means that, in 4 of these 42 patients, 2 lesions per patient were discovered. PET/CT also detected 46 abnormal findings, but only 43 were correctly recognized, whereas the other 3 were false-positive (FP). Six lesions could not be detected correctly: 3 were FP and 3 false-negative, which resulted in a sensitivity of 93.5% and a specificity of 97.5%. The site-specific evaluation showed 18 true-positive enlarged parathyroid glands with MRI, but also produced 13 FP findings and failed to detect 28 lesions; the sensitivity and specificity are thus 39.1% and 89.3%, respectively. The difference in detection rate between 18F-choline PET/CT and MRI was statistically significant (P < 0.001).

Conclusions

18F-choline PET/CT is clearly superior to MRI for localization diagnostics in primary hyperparathyroidism. Image fusion of both modalities can be helpful for more precise anatomical assignment.
FDG PET/CT in Isolated Spermatic Cord Metastasis From Colon Cancer
Authors: Ji Xia , Dong Aisheng 
Published: June 2021

Abstract
Isolated spermatic cord metastasis is extremely rare. We describe FDG PET/CT findings in a case of isolated spermatic cord metastasis from colon cancer detected 27 months after colectomy. The tumor showed intense focal FDG uptake in the right spermatic cord mimicking a primary spermatic cord malignancy.
A functionally distinct neutrophil landscape in severe COVID-19 reveals opportunities for adjunctive therapies
Authors: Panda Rachita , Silva Castanheira Fernanda Vargas E , Schlechte Jared , Surewaard Bas GJ , Shim Hanjoo Brian , Zucoloto Amanda Z , Slavikova Zdenka , Yipp Bryan G , Kubes Paul , McDonald Braedon 
Published: June 2021

ABSTRACTAcute respiratory distress syndrome (ARDS) is a life-threatening syndrome of respiratory failure and diffuse alveolar damage that results from dysregulated local and systemic immune activation, causing pulmonary vascular, parenchymal and alveolar damage. SARS-CoV-2 infection has become the dominant cause of ARDS worldwide, and emerging evidence implicates neutrophils and their cytotoxic arsenal of effector functions as central drivers of immune-mediated lung injury in COVID-19 ARDS. However, a key outstanding question is whether COVID-19 drives a unique program of neutrophil activation or effector functions that contributes to the severe pathogenesis of this pandemic illness, and whether this unique neutrophil response can be targeted to attenuate disease. Using a combination of high-dimensional single cell analysis and ex vivo functional assays of neutrophils from patients with COVID-19 ARDS compared to non-COVID ARDS (caused by bacterial pneumonia), we identified a functionally distinct landscape of neutrophil activation in COVID-19 ARDS that was intrinsically programmed during SARS-CoV-2 infection. Furthermore, neutrophils in COVID-19 ARDS were functionally primed to produce high amounts of neutrophil extracellular traps (NETs). Surprisingly, this unique pathological program of neutrophil priming escaped conventional therapy with dexamethasone, thereby revealing a promising target for adjunctive immunotherapy in severe COVID-19.
Complement activation induces excessive T cell cytotoxicity in severe COVID-19
Authors: Georg Philipp , Astaburuaga-García Rosario , Bonaguro Lorenzo , Brumhard Sophia , Michalick Laura , Lippert Lena J. , Kostevc Tomislav , Gäbel Christiane , Schneider Maria , Streitz Mathias , Demichev Vadim , Gemünd Ioanna , Barone Matthias , Tober-Lau Pinkus , Helbig Elisa Theresa , Stein Julia , Dey Hannah-Philine , Paclik Daniela , Mülleder Michael , Aulakh Simran Kaur , Mei Henrik E. , Schulz Axel R. , Hippenstiel Stefan , Corman Victor Max , Beule Dieter , Wyler Emanuel , Landthaler Markus , Obermayer-Wasserscheid Benedikt , Boor Peter , Demir Münevver , Wesselmann Hans , Suttorp Norbert , Uhrig Alexander , Müller-Redetzky Holger , Nattermann Jacob , Kuebler Wolfgang M. , Meisel Christian , Ralser Markus , Schultze Joachim L. , Aschenbrenner Anna C. , Thibeault Charlotte , Kurth Florian , Sander Leif-Erik , Blüthgen Nils , Sawitzki Birgit 
Published: June 2021

SummarySevere COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathogenesis, and it remains unclear if T cells also contribute to disease pathology. Here, we combined single-cell transcriptomics and proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly activated, CD16+ T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune complex-mediated, T cell receptor-independent degranulation and cytotoxicity not found in other diseases. CD16+ T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD16+ T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Age-dependent generation of C3a in severe COVID-19 induced activated CD16+ cytotoxic T cells. The proportion of activated CD16+ T cells and plasma levels of complement proteins upstream of C3a correlated with clinical outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19.
Microstructural variation in the human striatum using non-negative matrix factorization
Authors: Robert Corinne , Patel Raihaan , Blostein Nadia , Steele Chrisopher C. , Chakravarty M. Mallar 
Published: June 2021

AbstractThe striatum is a major subcortical connection hub that has been heavily implicated in a wide array of motor and cognitive functions. Here, we developed a normative multimodal, data-driven microstructural parcellation of the striatum using multiple magnetic resonance imaging-based metrics (mean diffusivity, fractional anisotropy, and the ratio between T1- and T2-weighted structural) from the Human Connectome Project Young Adult dataset (n=329 unrelated participants, age range: 22-35, F/M: 185/144). We further explored the biological and functional relationships of this parcellation by relating our findings to motor and cognitive performance in tasks known to involve the striatum as well as demographics. We identified 5 spatially distinct striatal components, for each hemisphere. We also show the gain in component stability when using multimodal versus unimodal metrics. Our findings suggest distinct microstructural patterns in the human striatum that are largely symmetric and that relate mostly to age and sex. Our work also highlights the putative functional relevance of these striatal components to different designations based on a Neurosynth meta-analysis.