bluuebunny/crossref_metadata_2025 huggingface dataset:
An energy-conserving dynamical model of GRB afterglows from magnetized forward and reverse shocks
Authors: Chen Qiang , Liu Xue-Wen
Published: April 2021

In the dynamical models of gamma-ray burst (GRB) afterglows, the uniform assumption of the shocked region is known as provoking total energy conservation problem. In this work, we consider shocks originating from magnetized ejecta and extend the energy-conserving hydrodynamical model of Yan, Wei & Fan to the MHD limit by applying the magnetized jump conditions from Zhang & Kobayashi. Compared with the non-conservative models, our Lorentz factor of the whole shocked region is larger by a factor ${\lesssim}\sqrt{2}$. The total pressure of the forward shocked region is higher than the reversed shocked region, in the relativistic regime with a factor of about 3 in our interstellar medium (ISM) cases while ejecta magnetization degree σ < 1, and a factor of about 2.4 in the wind cases. For σ ≤ 1, the non-conservative model loses 32–42 per cent of its total energy for ISM cases, and for wind cases 25–38 per cent, which happens specifically in the forward shocked region, making the shock synchrotron emission from the forward shock less luminous than expected. Once the energy conservation problem is fixed, the late-time light curves from the forward shock become nearly independent of the ejecta magnetization. The reverse shocked region does not suffer from the energy conservation problem since the changes of the Lorentz factor are recompensed by the changes of the shocked particle number density. The early light curves from the reverse shock are sensitive to the magnetization of the ejecta, thus are an important probe of the magnetization degree.
Bimodal regulation of the PRC2 complex by USP7 underlies tumorigenesis
Authors: Su Dongxue , Wang Wenjuan , Hou Yongqiang , Wang Liyong , Yi Xianfu , Cao Cheng , Wang Yuejiao , Gao Huan , Wang Yue , Yang Chao , Liu Beibei , Chen Xing , Wu Xiaodi , Wu Jiajing , Yan Dong , Wei Shuqi , Han Lulu , Liu Shumeng , Wang Qian , Shi Lei , Shan Lin
Published: April 2021

Although overexpression of EZH2, a catalytic subunit of the polycomb repressive complex 2 (PRC2), is an eminent feature of various cancers, the regulation of its abundance and function remains insufficiently understood. We report here that the PRC2 complex is physically associated with ubiquitin-specific protease USP7 in cancer cells where USP7 acts to deubiquitinate and stabilize EZH2. Interestingly, we found that USP7-catalyzed H2BK120ub1 deubiquitination is a prerequisite for chromatin loading of PRC2 thus H3K27 trimethylation, and this process is not affected by H2AK119 ubiquitination catalyzed by PRC1. Genome-wide analysis of the transcriptional targets of the USP7/PRC2 complex identified a cohort of genes including FOXO1 that are involved in cell growth and proliferation. We demonstrated that the USP7/PRC2 complex drives cancer cell proliferation and tumorigenesis in vitro and in vivo. We showed that the expression of both USP7 and EZH2 elevates during tumor progression, corresponding to a diminished FOXO1 expression, and the level of the expression of USP7 and EZH2 strongly correlates with histological grades and prognosis of tumor patients. These results reveal a dual role for USP7 in the regulation of the abundance and function of EZH2, supporting the pursuit of USP7 as a therapeutic target for cancer intervention.
HPF1-dependent PARP activation promotes LIG3-XRCC1-mediated backup pathway of Okazaki fragment ligation
Authors: Kumamoto Soichiro , Nishiyama Atsuya , Chiba Yoshie , Miyashita Ryota , Konishi Chieko , Azuma Yoshiaki , Nakanishi Makoto
Published: April 2021

DNA ligase 1 (LIG1) is known as the major DNA ligase responsible for Okazaki fragment joining. Recent studies have implicated LIG3 complexed with XRCC1 as an alternative player in Okazaki fragment joining in cases where LIG1 is not functional, although the underlying mechanisms are largely unknown. Here, using a cell-free system derived from Xenopus egg extracts, we demonstrated the essential role of PARP1-HPF1 in LIG3-dependent Okazaki fragment joining. We found that Okazaki fragments were eventually ligated even in the absence of LIG1, employing in its place LIG3-XRCC1, which was recruited onto chromatin. Concomitantly, LIG1 deficiency induces ADP-ribosylation of histone H3 in a PARP1-HPF1-dependent manner. The depletion of PARP1 or HPF1 resulted in a failure to recruit LIG3 onto chromatin and a subsequent failure in Okazaki fragment joining in LIG1-depleted extracts. Importantly, Okazaki fragments were not ligated at all when LIG1 and XRCC1 were co-depleted. Our results suggest that a unique form of ADP-ribosylation signaling promotes the recruitment of LIG3 on chromatin and its mediation of Okazaki fragment joining as a backup system for LIG1 perturbation.
What makes a type IIA topoisomerase a gyrase or a Topo IV?
Authors: Hirsch Jana , Klostermeier Dagmar
Published: April 2021

Type IIA topoisomerases catalyze a variety of different reactions: eukaryotic topoisomerase II relaxes DNA in an ATP-dependent reaction, whereas the bacterial representatives gyrase and topoisomerase IV (Topo IV) preferentially introduce negative supercoils into DNA (gyrase) or decatenate DNA (Topo IV). Gyrase and Topo IV perform separate, dedicated tasks during replication: gyrase removes positive supercoils in front, Topo IV removes pre-catenanes behind the replication fork. Despite their well-separated cellular functions, gyrase and Topo IV have an overlapping activity spectrum: gyrase is also able to catalyze DNA decatenation, although less efficiently than Topo IV. The balance between supercoiling and decatenation activities is different for gyrases from different organisms. Both enzymes consist of a conserved topoisomerase core and structurally divergent C-terminal domains (CTDs). Deletion of the entire CTD, mutation of a conserved motif and even by just a single point mutation within the CTD converts gyrase into a Topo IV-like enzyme, implicating the CTDs as the major determinant for function. Here, we summarize the structural and mechanistic features that make a type IIA topoisomerase a gyrase or a Topo IV, and discuss the implications for type IIA topoisomerase evolution.
High-Speed Excitation-Spectral Microscopy Uncovers In Situ Rearrangement of Light-Harvesting Apparatus in Chlamydomonas during State Transitions at Submicron Precision
Authors: Zhang Xian Jun , Fujita Yuki , Tokutsu Ryutaro , Minagawa Jun , Ye Shen , Shibata Yutaka
Published: April 2021

Photosynthetic organisms adjust to fluctuating natural light under physiological ambient conditions through flexible light-harvesting ability of light-harvesting complex II (LHCII). A process called state transition is an efficient regulation mechanism to balance the excitations between photosystem II (PSII) and photosystem I (PSI) by shuttling mobile LHCII between them. However, in situ observation of the migration of LHCII in vivo remains limited. In this study, we investigated the in vivo reversible changes in the intracellular distribution of the chlorophyll (Chl) fluorescence during the light-induced state transitions in Chlamydomonas reinhardtii. The newly developed noninvasive excitation-spectral microscope provided powerful spectral information about excitation-energy transfer between Chl-a and Chl-b. The excitation spectra were detected through the fluorescence emission in the 700–750-nm spectral range, where PSII makes the main contribution, though PSI still makes a non-negligible contribution at room temperature. The technique is sensitive to the Chl-b spectral component specifically bound to LHCII. Using a PSI-specific 685-nm component also provided visualization of the local relative concentration of PSI within a chloroplast at room temperature. The decrease in the relative intensity of the Chl-b band in state 2 was more conspicuous in the PSII-rich region than in the PSI-rich region, reflecting the dissociation of LHCII from PSII. We observed intracellular redistributions of the Chl-b-related light-harvesting abilities within a chloroplast during the state transitions. This observation implies the association of the state transitions with the morphological changes in the thylakoid membrane.
A single-cell view of the transcriptome during lateral root initiation inArabidopsis thaliana
Authors: Gala Hardik P. , Lanctot Amy , Jean-Baptiste Ken , Guiziou Sarah , Chu Jonah C. , Zemke Joseph E. , George Wesley , Queitsch Christine , Cuperus Josh T. , Nemhauser Jennifer L.
Published: April 2021

Root architecture is a major determinant of plant fitness and is under constant modification in response to favorable and unfavorable environmental stimuli. Beyond impacts on the primary root, the environment can alter the position, spacing, density, and length of secondary or lateral roots. Lateral root development is among the best-studied examples of plant organogenesis, yet there are still many unanswered questions about its earliest steps. Among the challenges faced in capturing these first molecular events is the fact that this process occurs in a small number of cells with unpredictable timing. Single-cell sequencing methods afford the opportunity to isolate the specific transcriptional changes occurring in cells undergoing this fate transition. Using this approach, we successfully captured the transcriptomes of initiating lateral root primordia in Arabidopsis thaliana and discovered many upregulated genes associated with this process. We developed a method to selectively repress target gene transcription in the xylem pole pericycle cells where lateral roots originate and demonstrated that the expression of several of these targets is required for normal root development. We also discovered subpopulations of cells in the pericycle and endodermal cell files that respond to lateral root initiation, highlighting the coordination across cell files required for this fate transition.
Profile of Mood States Factor Structure Does Not Accurately Account for Patients with Chronic Pain
Authors: López-Jiménez Celia María , Cano-García Francisco Javier , Sanduvete-Chaves Susana , Chacón-Moscoso Salvador
Published: April 2021

Objective

The need for measuring emotional functioning in patients with chronic pain was recognized decades ago. The Initiative on Methods, Measures, and Pain Assessment in Clinical Trials (IMMPACT) proposed the Profile of Mood States for this purpose. However, to date, its factor structure has not been confirmed in these patients.

Methods

We set out to use confirmatory factor analysis to test the theoretical structure of seven factors: Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, Confusion-Bewilderment, and Friendliness.

Participants

The sample consisted of 588 Spanish adult patients with chronic pain.

Results

The original structure could not be verified according to the obtained fit indices (e.g., root-mean-square error of approximation = 0.11). For this reason, we carried out a second study that relied on exploratory factor analysis to evaluate the structure in half of the cases and confirmatory factor analysis to validate it in the other half. The factor structure detected in the exploratory factor analysis was not satisfactory, nor could it be validated with confirmatory factor analysis (e.g., normed fit index between 0.54 and 0.56).

Conclusions

The factor structure of the Profile of Mood States could not be satisfactorily confirmed. Consequently, other mood measures and shorter, optimized versions of the POMS are discussed as possible alternatives.
Molecular flexibility in computational protein design: an algorithmic perspective
Authors: Bouchiba Younes , Cortés Juan , Schiex Thomas , Barbe Sophie
Published: April 2021

Computational protein design (CPD) is a powerful technique for engineering new proteins, with both great fundamental implications and diverse practical interests. However, the approximations usually made for computational efficiency, using a single fixed backbone and a discrete set of side chain rotamers, tend to produce rigid and hyper-stable folds that may lack functionality. These approximations contrast with the demonstrated importance of molecular flexibility and motions in a wide range of protein functions. The integration of backbone flexibility and multiple conformational states in CPD, in order to relieve the inaccuracies resulting from these simplifications and to improve design reliability, are attracting increased attention. However, the greatly increased search space that needs to be explored in these extensions defines extremely challenging computational problems. In this review, we outline the principles of CPD and discuss recent effort in algorithmic developments for incorporating molecular flexibility in the design process.
Using Treatment Fidelity Measures to Understand Walking Recovery: A Secondary Analysis From the Community Ambulation Project
Authors: Mangione Kathleen K , Posner Michael A , Craik Rebecca L , Wolff Edward F , Fortinsky Richard H , Beamer Brock A , Binder Ellen F , Orwig Denise L , Magaziner Jay , Resnick Barbara
Published: April 2021

Objectives

Physical therapist intervention studies can be deemed ineffective when, in fact, they may not have been delivered as intended. Measurement of treatment fidelity (TF) can address this issue. The purpose of this study was to describe TF of a home-based intervention, identify factors associated with TF, and examine whether components of TF were associated with the outcome of change in 6-minute walk distance (∆6MWD).

Methods

This is a secondary analysis of community-dwelling hip fracture participants who completed standard therapy and were randomly assigned to the active intervention (Push). Push was 16 weeks of lower extremity strengthening, function, and endurance training. TF was defined as delivery (attendance rate, exercise duration) and receipt (progression in training load, heart rate reserve [HRR] during endurance training, and exercise position [exercise on floor]). The outcome was ∆6MWD. Independent variables included baseline (demographic and clinical) measures. Descriptive statistics were calculated; linear and logistic regressions were performed.

Results

Eighty-nine participants were included in this analysis; 59 (66%) had attendance of 75% or greater. Participants walked for 20 minutes or more for 78% of sessions. The average training load increased by 22%; the mean HRR was 35%; and 61 (69%) participants exercised on the floor for at least 75% of sessions. Regression analyses showed that a higher body mass index and greater baseline 6MWD were related to components of TF; 4 out of 5 components of TF were significantly related to ∆6MWD. The strongest TF relationship showed that those who exercised on the floor improved by 62 m (95% CI = 31–93 m) more than those who did not get on the floor.

Conclusions

Measures of TF should extend beyond attendance rate. This analysis demonstrates how measures of TF, including program attendance, progression in training load, endurance duration, and exercising on the floor were significantly related to improvement in 6MWD in participants post hip fracture.

Impact

This careful analysis of treatment fidelity assured that the intervention was delivered and received as intended. Analysis of data from a large trial with participants after hip fracture showed that regular attendance, frequent endurance training for 20 minutes, increases in lower extremity training loads, and exercising on the floor were associated with improvements in the outcome of 6-minute-walk distance. The strongest association with improvement was exercising on the floor.
Unravelling resilience mechanisms in forests: role of non-structural carbohydrates in responding to extreme weather events
Authors: D’Andrea Ettore , Scartazza Andrea , Battistelli Alberto , Collalti Alessio , Proietti Simona , Rezaie Negar , Matteucci Giorgio , Moscatello Stefano
Published: April 2021

Extreme weather events are increasing in frequency and intensity due to global climate change. We hypothesized that tree carbon reserves are crucial for resilience of beech, buffering the source–sink imbalance due to late frosts and summer droughts, and that different components of non-structural carbohydrates (NSCs) play specific roles in coping with stressful situations. To assess the compound effects on mature trees of two extreme weather events, first a late frost in spring 2016 and then a drought in summer 2017, we monitored the phenology, radial growth and the dynamics of starch and soluble sugars in a Mediterranean beech forest. A growth reduction of 85% was observed after the spring late frost, yet not after the drought event. We observed a strong impact of late frost on starch, which also affected its dynamic at the beginning of the subsequent vegetative season. In 2017, the increase of soluble sugars, associated with starch hydrolysis, played a crucial role in coping with the severe summer drought. Non-structural carbohydrates helped to counteract the negative effects of both events, supporting plant survival and buffering source–sink imbalances under stressful conditions. Our findings indicate a strong trade-off between growth and NSC storage in trees. Overall, our results highlight the key role of NSCs on beech trees, response to extreme weather events, confirming the resilience of this species to highly stressful events. These insights are useful for assessing how forests may respond to the potential impacts of climate change on ecosystem processes in the Mediterranean area.
Clinical and Epidemiological Characteristics of Paediatric Patients Diagnosed with COVID-19 in a Tertiary Hospital in Mexico City
Authors: Macias-Parra Mercedes , Fortes-Gutierrez Sofia , Aguilar-Gomez Nancy , Diaz-Garcia Luisa , Otero-Mendoza Francisco , Arias de la Garza Eduardo , Ordoñez-Ortega Javier , Palacios-Reyes Debora , Diaz-Jimenez Irma Virginia , Serrano-Sierra Alejandro , Xochihua-Díaz Luis , Saltigeral-Simental Patricia
Published: April 2021

COVID-19 affects the paediatric population less frequently than adults. A retrospective study was performed in a tertiary paediatric hospital in Mexico City in children <18 years of age who were hospitalized with a positive reverse transcription-polymerase chain reaction for SARS-CoV-2. Included in the study were 86 patients with a median age of 10 years old (IQR 2.6–14.3 years), who were classified in three groups: previously healthy, with chronic disease and immunosuppressed patients. The principal signs and symptoms were fever (81%), cough (51%) and headache (35%). A total of 20 patients (23%) required management in the paediatric intensive care unit (PICU) and 17% needed mechanical ventilation for an average of 12.7 days (IQR 2–29 days). There was no statistically significant difference between the three clinical classification groups in those patients admitted to the PICU, most of which were previously healthy patients. The mortality rate was 5% (four patients). Given that the paediatric population is susceptible to infection, potential transmitters and to clinical presentations with variable degrees of severity, it is important to continue reinforcing social distancing measures.
Special, Personal and Broad Expression: Exploring Freedom of Expression Norms under the General Data Protection Regulation
Authors: Erdos David
Published: April 2021

The interface between data protection and freedom of expression is increasingly crucial and the General Data Protection Regulation (GDPR) solidifies a bipartite or potentially even tripartite conceptualization of this relationship. Whilst the GDPR’s personal exemption can play some role in governing individual expression, it must be construed narrowly so as to only exclude innocuous publication that is not liable to infringe other’s fundamental rights. The special expression derogation remains central and encompasses not just journalism but also other forms of special expression (academic, artistic, literary) which, when published, are objectively orientated towards a collective public. Whilst Member States do retain considerable discretion given the wide diversity of national constitutional norms in this area, a strict balancing between fundamental rights should still be ensured. Freedom of expression is also distinctly furthered by, inter alia, self-expression on social networking sites and the facilitation of a range of expressive purposes by search engines. As shown in GC and Others v CNIL, the stricter reconciliation of rights here must retain a direct role for data protection’s core substance including its legal grounds and principles and is thereby substantially (albeit not completely) harmonized across the EU.
The Single Accreditation System: Risks to the Osteopathic Profession
Authors: Cummings Mark
Published: April 2021

In August 2014, the American Osteopathic Association (AOA) and the American Association of Colleges of Osteopathic Medicine (AACOM) signed a memorandum of understanding with the Accreditation Council for Graduate Medical Education (ACGME) to create the Single Accreditation System (SAS) for graduate medical education (GME) in the United States. The AOA made the decision that it would close its GME accreditation system in response to dramatic growth in colleges of osteopathic medicine, a shortfall in osteopathic GME positions with increasing dependence on the ACGME system, ACGME policy decisions that adversely impacted osteopathic students, and declining osteopathic student interest in primary care.

Osteopathic teaching institutions bore responsibility for meeting ACGME accreditation standards between 2015 and 2020, including determining institutional sponsorship, which program applications to submit, program size, educational leadership, and whether to pursue Osteopathic Recognition. Approximately 692 of 954 (72.5%) eligible osteopathic GME programs in 2014–2015 obtained ACGME accreditation by June 1, 2020. There were sharp reductions in surgical and subspecialty programs and a significant drop of DOs in educational leadership positions. A low percentage of ACGME-accredited programs applied for Osteopathic Recognition.

In closing its GME accreditation system and joining the ACGME, the AOA gave up control of its direct relationship with osteopathic residents, fellows, and teaching institutions to gain critical GME opportunities. In this article, the author considers whether this gain will offset the risks taken by the AOA, including decreased DO leadership opportunities and role models, lower than expected interest in Osteopathic Recognition, and possible decreased DO interest in osteopathic organizations and osteopathic specialty board certification. Time and the choices of current and future DO trainees in ACGME programs will determine the future of the osteopathic profession—and whether these risks were worth taking.
The ACGME Single Accreditation System: Alterations in the Force of Graduate Medical Education
Authors: Nasca Thomas J. , Miller Rebecca , Brigham Timothy P.
Published: April 2021

The Accreditation Council for Graduate Medical Education (ACGME), the American Osteopathic Association (AOA), and the American Association of Colleges of Osteopathic Medicine (AACOM) disturbed the gravitational forces of medical education when they entered into a historic agreement in August 2014. This agreement resulted in a 6-year journey to a single accreditation pathway for all residency programs and nearly all fellowship programs in the United States. It brought together the 2 traditions of medicine in the country for the first time in more than 100 years, unifying a critical phase of medical education for all physicians in the United States. In this commentary, the authors briefly describe the Single Accreditation System and relate their perspective on the factors leading to this profoundly important event and its impact on the ACGME, AOA, and medical education.
Visceral fat is associated with high-grade complications in patients undergoing minimally invasive partial nephrectomy for small renal masses
Authors: Nesbitt Kelan , Sharma Pranav
Published: April 2021

Introduction:

Minimally invasive partial nephrectomy is standard of care treatment for small renal masses.

Objective:

We evaluated the relationship between subcutaneous and visceral obesity with high-grade postoperative 30-day complications in patients undergoing minimally invasive partial nephrectomy.

Methods:

We retrospectively identified 98 patients at our institution from 2014 to 2017 who underwent laparoscopic or robotic-assisted partial nephrectomy due to suspected renal cell carcinoma. Patients were stratified based on presence or absence of high-grade (Clavien ≥ IIIa) 30-day postoperative complications. Means were compared with the independent t test and proportions with chi-square analysis. Multivariate logistic regression was performed to determine independent predictors of high-grade 30-day complications.

Results:

Mean nephrometry score was 6.7 with 21 (21.4%) patients having hilar tumors. Mean estimation of blood loss was 207 mL, mean operating time was 223 min, and mean warm ischemia time was 23 min. The majority of patients had clear renal cell carcinoma (n = 83, 84.7%) and pT1a disease (n = 76, 77.6%) with negative margins (n = 89, 90.8%) on pathology. There were 5 (5.1%) patients who experienced a high-grade postoperative 30-day complication. Mean visceral fat index was an independent predictor of high-grade 30-day complications (odds ratio: 1.02; 95% confidence interval: 1.002–1.03; p = 0.027).

Conclusions:

Visceral obesity should be considered as a prognostic indicator of outcomes in patients undergoing surgical treatment for a small renal mass.
Lunar cycle, seasonal variation, and prevalence of emergency urological presentations: correlation or coincidence?—A preliminary report
Authors: Akinpelu Tosin S. , Laher Abdullah E. , Chen Andrew , Adam Ahmed
Published: April 2021

Objective:

The objective of this study was to conduct a pilot study to determine the prevalence and patterns of emergency urological presentations and to evaluate their relationship with the lunar cycle and seasonal variation.

Methods:

Medical records of subjects that presented with urological pathology to the Emergency Department during the 2017 calendar year were retrospectively reviewed. The data extracted included demographic details, date and day of presentation, presenting complaints, investigations, radiological findings, and final diagnosis. Associations between emergent presentations and the lunar phase and seasonal variation were determined.

Results:

A total of 199 subjects were enrolled. The median participant age was 49 (interquartile range 31–64) years with the majority (n = 136, 68.3%) being male. Cystitis (n = 55, 27.6%), prostate cancer (n = 30, 15.1%), benign prostatic hypertrophy (n = 29, 14.6%), and urolithiasis (n = 29, 14.6%) were the most common clinical diagnosis. There were 96 (48.2%) patients who presented during the waxing moon phase, whereas 85 (42.7%) presented during the waning moon phase, 11 (5.6%) presented on the day of full moon, and 7 (3.5%) patients presented on the day of the new moon. Most patients presented during the summer months (n = 61, 30.7%). There was no significant association between the lunar cycle and emergent urological presentations (p = 0.99).

Conclusion:

In this pilot study, there was no significant association between the lunar cycle and emergent urological presentations. However, during the summer months more urology-related emergency presentations to the Emergency Department were observed.
A prospective study of the effect of testosterone escape on preradiotherapy prostate-specific antigen kinetics in prostate cancer patients undergoing neoadjuvant androgen deprivation therapy
Authors: Christie David R.H. , Mitina Natalia , Sharpley Christopher F.
Published: April 2021

Introduction:

Prostate-specific antigen (PSA) kinetic patterns during neoadjuvant androgen deprivation therapy have been shown to predict unfavorable long-term outcomes.

Objective:

To investigate the effect of testosterone escape (TE) on these kinetic patterns, as this had not been previously reported.

Methods:

There were 50 consecutive prostate cancer patients who received 6 months of triptorelin prior to definitive radiotherapy (RT). Testosterone and PSA levels were measured at baseline and every 6 weeks. Clinical factors were tested for their ability to predict for TE and unfavorable PSA kinetic patterns. The effects of TE, at both 1.7 and 0.7 nmol/L levels, were analyzed.

Results:

TE occurred in at least one reading for 14% and 34% of the patients at the 1.7 and 0.7 nmol/L levels, respectively. No baseline factors predicted TE. The median PSA halving time was 25 days and the median pre-RT PSA level was 0.55 ng/mL. The only factor significantly associated with a higher pre-RT PSA level was a higher baseline PSA level. The only factor that significantly predicted a longer PSA halving time was TE at the 1.7 nmol/L level.

Conclusions:

TE and higher baseline PSA levels may adversely affect PSA kinetics and other outcomes for patients undergoing neoadjuvant hormone therapy prior to radiotherapy. Studies investigating the tailoring of neoadjuvant therapy by extending the duration in those patients with a higher baseline PSA level or by the addition of anti-androgens in those demonstrating TE, should be considered.
Bladder preservation versus radical cystectomy in transitional cell carcinoma and squamous cell carcinoma muscle invasive bladder cancer
Authors: Mohamed Dalia O. , Sayed Mona M. , Abdelkawi Islam F. , Elshoieby Mahmoud H. , Khallaf Salah M. , Khallaf Lamia M. , Fouad Doaa M.
Published: April 2021

Background:

Randomizing patients to bladder preservation or radical cystectomy (RC) for the treatment of bladder cancer has not been practical, due to patient and physician preferences. Therefore, continually comparing the 2 treatment modalities is needed, in order to make the proper choice for each patient.

Patients and methods:

The records of T1–4N0M0 bladder cancer patients, who presented to the South Egypt Cancer Institute between 2007 and 2017 and were treated by either bladder preservation or RC were reviewed.

Results:

Out of the 166 included patients, 81 (48.8%) patients were treated by bladder preservation and 85 (51.2%) patients had RC. For the patients treated by bladder preservation and the patients treated by RC, the 5-year overall survival (OS) was 56% and 60% (p = 0.67), the 5-year local recurrence-free survival was 69% and 73% (p = 0.69), and the 5-year disease-free survival was 45% and 53% (p = 0.16), respectively. After propensity matching analysis, the mean 5-year OS was 58% for the bladder preservation patients and 61% for the RC patients (p = 0.51). It is notable that among the bladder preservation group, 8 patients (10%) had squamous cell carcinoma (SCC) pathology and refused RC. Their OS was 56% compared to 53% for the SCC patients treated by RC (p = 0.6).

Conclusion:

Bladder preservation is a safe alternative to cystectomy in transitional cell carcinoma stages T1–4aN0M0, and its use in SCC bladder cancer should be further studied, as it could be feasible to spare them from initial cystectomy.
Activation of the dorsal, but not the ventral, hippocampus relieves neuropathic pain in rodents
Authors: Wei Xuhong , Centeno Maria Virginia , Ren Wenjie , Borruto Anna Maria , Procissi Daniele , Xu Ting , Jabakhanji Rami , Mao Zuchao , Kim Haram , Li Yajing , Yang Yiyuan , Gutruf Philipp , Rogers John A. , Surmeier D. James , Radulovic Jelena , Liu Xianguo , Martina Marco , Apkarian Apkar Vania
Published: April 2021

Accumulating evidence suggests hippocampal impairment under the chronic pain phenotype. However, it is unknown whether neuropathic behaviors are related to dysfunction of the hippocampal circuitry. Here, we enhanced hippocampal activity by pharmacological, optogenetic, and chemogenetic techniques to determine hippocampal influence on neuropathic pain behaviors. We found that excitation of the dorsal (DH), but not the ventral (VH) hippocampus induces analgesia in 2 rodent models of neuropathic pain (SNI and SNL) and in rats and mice. Optogenetic and pharmacological manipulations of DH neurons demonstrated that DH-induced analgesia was mediated by N-Methyl-D-aspartate and μ-opioid receptors. In addition to analgesia, optogenetic stimulation of the DH in SNI mice also resulted in enhanced real-time conditioned place preference for the chamber where the DH was activated, a finding consistent with pain relief. Similar manipulations in the VH were ineffective. Using chemo-functional magnetic resonance imaging (fMRI), where awake resting-state fMRI was combined with viral vector-mediated chemogenetic activation (PSAM/PSEM89s) of DH neurons, we demonstrated changes of functional connectivity between the DH and thalamus and somatosensory regions that tracked the extent of relief from tactile allodynia. Moreover, we examined hippocampal functional connectivity in humans and observe differential reorganization of its anterior and posterior subdivisions between subacute and chronic back pain. Altogether, these results imply that downregulation of the DH circuitry during chronic neuropathic pain aggravates pain-related behaviors. Conversely, activation of the DH reverses pain-related behaviors through local excitatory and opioidergic mechanisms affecting DH functional connectivity. Thus, this study exhibits a novel causal role for the DH but not the VH in controlling neuropathic pain–related behaviors.
A Quality Improvement Project for Monitoring Surgical Patients With Obstructive Sleep Apnea
Authors: Fotino Karen
Published: April 2021

Introduction

Patients who have obstructive sleep apnea (OSA) are at a higher risk for opioid-induced respiratory depression postoperatively. Many patients who have OSA are not given a diagnosis before undergoing surgery and may not be monitored appropriately afterward.

Purpose

The purpose of this quality improvement project was to increase the number of preoperative patients screened for OSA and improve their postoperative monitoring through a novel OSA protocol order set through the implementation of evidence-based practices.

Methods

Screening for OSA risk is performed preoperatively using the STOP-Bang instrument. High-risk patients, as well as patients with existing OSA, are monitored postoperatively using a bundle of evidence practices to identify early respiratory compromise. If respiratory events occur, a treatment intervention will be triggered.

Outcome

Postintervention chart reviews demonstrated 100% of the qualifying patients had OSA screening completed before surgery. The OSA protocol was ordered in 28 of the 100 charts reviewed. Patient harm may have been avoided through the implementation of the protocol's standing order for continuous positive airway pressure, which was triggered by respiratory events.

Conclusion

It is important to identify these high-risk patients before surgery through preoperative screening. These patients should be monitored closely postoperatively to identify early respiratory compromise.
Pain Quality Among Hospitalized Postcraniotomy Brain Tumor Patients
Authors: Foust Winton Rebecca E. , Draucker Claire B. , Von Ah Diane
Published: April 2021

Purpose/Aims

The aim of this study was to describe how persons given a diagnosis of a brain tumor who have had a craniotomy describe the quality of their pain after surgery.

Design

A qualitative descriptive design was used.

Methods

Qualitative descriptive methods as described by Sandelowski guided this study. Semistructured interviews were conducted with patients hospitalized on a neurological step-down unit in an urban teaching hospital in the Midwestern United States. Interviews focused on the quality of participants' pain after surgery. Narratives were analyzed using standard content analysis.

Results

Twenty-seven participants were interviewed. Most were White and female. Most underwent a craniotomy using an anterior approach with sedation. Participants described the quality of their pain with 6 different types of descriptors: pain as pressure, pain as tender or sore, pain as stabbing, pain as throbbing, pain as jarring, and pain as itching.

Conclusions

Participants' descriptions of their pain quality after surgery provide a different understanding than do numerical pain ratings. Clinicians should use questions to explore patients' individual pain experiences, seeking to understand the quality of patients' pain and their perceptions.
Lumbar Bracing for Chronic Low Back Pain
Authors: Annaswamy Thiru M. , Cunniff Kegan J. , Kroll Mitchell , Yap Lori , Hasley Matthew , Lin Chung-Kuang , Petrasic Jason
Published: April 2021

Purpose

We performed this study to evaluate the effect of back bracing to treat patients with chronic low back pain.

Methods

This was a prospective, unblinded, randomized controlled trial of 61 adults with uncomplicated chronic low back pain (>12 wks) and imaging findings of degenerative spondylosis, to assess the effectiveness of a semirigid back brace. All study participants received back school instruction. The treatment group also received a lumbar orthosis and was instructed to wear it as needed for symptom relief. At baseline, 6 wks, 12 wks, and 6 mos after intervention, we collected: Numerical Rating Scale to measure pain intensity, Pain Disability Questionnaire, Patient-Reported Outcome Measurement Information System, and EuroQol 5-Dimension (EQ-5D) to measure patient-reported function and quality of life.

Results

An interim analysis at the halfway point in enrollment (61 of 120 planned participants) revealed the Pain Disability Questionnaire, Patient-Reported Outcome Measurement Information System, and EQ-5D scores in the treatment group to be worse than in the control group, but no significant group differences in Numerical Rating Scale scores. Outcome differences between groups analyzed over time revealed (effect [P]): Pain Disability Questionnaire = 0.84 (0.04); Patient-Reported Outcome Measurement Information System = 0.78 (0.005); EQ-5D = 0.06 (0.01); and Numerical Rating Scale = 0.02 (0.6). We halted the study because continuation was unlikely to produce significant changes to the results.

Conclusions

In patients with uncomplicated chronic low back pain, a back brace when combined with education and exercise instruction did not provide any pain relief compared with education and exercise instruction alone.

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CME Objectives

Upon completion of this article, the reader should be able to: (1) Describe the effect of lumbar back bracing on pain intensity in patients with chronic low back pain; (2) Discuss the effects of lumbar back bracing on pain-related disability, function, and quality of life in patients with chronic low back pain; and (3) Understand the role of lumbar back bracing in the treatment of patients with chronic low back pain.

Level

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The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
The Moderating Effects of Genetic Variations on Changes in Physical Activity Level and Cardiorespiratory Fitness in Response to a Life-Style Intervention: A Randomized Controlled Trial
Authors: Lee Harold H. , McGeary John E. , Dunsiger Shira , Baker Laura , Balasubramanyam Ashok , Knowler William C. , Williams David M.
Published: April 2021

Objective

Prior studies identified single nucleotide polymorphisms (SNPs) associated with physical activity (PA) level in a natural environment and intervention study: rs978656-DNAPTP6, rs10887741-PAPSS2, rs7279064-C18orf2, and rs6265-BDNF. Using the four SNPs’ polygenic score (PGS), we examined whether PGS moderates a life-style intervention’s effect on changes in PA level and cardiorespiratory fitness (CRF).

Methods

This is a secondary analysis of Look AHEAD, a multicenter randomized controlled trial designed to test the health benefits of a life-style intervention among 2675 participants with overweight/obesity and type 2 diabetes (ages, 45–76 years). Using linear mixed-effects models, level of PA (Paffenbarger PA questionnaire) and treadmill-assessed CRF were each regressed on four SNPs’ PGS, study time (baseline, year 1, and year 4), intervention arm, and interactions between the three. Models adjusted for age, sex, body mass index, ancestry principal components (population stratification), and study sites, with Bonferroni corrections for multiple testing (α < .005). Effect modification by age was examined.

Results

PGS was not predictive of change in CRF or PA level in response to intervention. In analyses without PGS by intervention by time, the relationships between PGS and PA phenotypes were modified by age (p interaction = .048 for CRF and .058 for PA), such that a 1-unit increase in PGS was associated with 24 kcal · wk−1 more in moderate-intensity PA and 0.004 MET higher CRF only among older groups (age >55 years for CRF, >60 years for PA level).

Conclusions

The effects of the intervention on PA and CRF were not moderated by the four SNPs. Future studies with extended SNP list should confirm the findings on effect modification by age.
Prevalence and Risk Factors for Anxiety and Depression in Patients With COVID-19 in Wuhan, China
Authors: Li Tao , Sun Siwei , Liu Bao , Wang Jing , Zhang Yalan , Gong Cheng , Duan Jun
Published: April 2021

Objective

Infectious diseases can cause psychological changes in patients. This study aimed to evaluate the prevalence and related risk factors for anxiety and depression in patients with COVID-19.

Methods

A cross-sectional study was performed on patients with COVID-19 admitted to the Sino-French New City branch of Wuhan Tongji Hospital from January to February 2020. The Zung Self-Rating Anxiety and Depression Scales were used to evaluate the prevalence of anxiety and depression. Demographic, clinical, and sociological data were also collected. Multivariable logistic regression analysis was used to identify independent risk factors of anxiety and depression in patients with COVID-19.

Results

In the current study, 183 patients were enrolled (mean age = 53 ± 9 years; 41.1% women). The prevalences of anxiety and depression were 56.3% and 39.3%, respectively. Logistic regression analysis revealed that older age, female sex, being divorced or widowed, COVID-19 disease duration, renal disease, and depression were identified as independent risk factors for anxiety in patients with COVID-19. Factors that were associated with depression were female sex, being widowed, COVID-19 disease duration, and anxiety.

Conclusions

This study demonstrates a high prevalence of anxiety and depression in patients with COVID-19 at the peak of the epidemic in Wuhan, China. The identification of demographic, clinical, and social factors may help identify health care professionals to provide psychological care as part of treatment for patients with COVID-19 and other life-threatening infectious diseases.
Evaluation of the Clinical Effectiveness of Shear Wave Elastography in Pediatric Cases With Acute Appendicitis
Authors: Isik İshak Abdurrahman , Ozkan Mehmet Burak
Published: April 2021

To determine sensitivity and specificity of shear wave elastography in pediatric patients diagnosed with acute inflammation of the appendix. Forty-eight patients who were referred for abdominal pain, with 18 volunteers recruited for the evaluation. Alvarado scores were calculated on the patients. The elasticity and stiffness of the inflamed appendix tissues of patients and controls were measured using shear wave elastography. The anterior, posterior, and medial parts of the appendix tissue were measured, calculating the highest elasticity values in kPa. In the end, 32 patients with Alvarado scores between 7 and 9 (group 1) underwent surgery, whereas 3 of them had pathological specimens reporting as normal. Eight of the patients whose Alvarado scores were between 4 and 6 and had inflammatory conditions of the appendix (group 2), plus the control group totaled 16 patients (group 3). The median shear wave value was found to be significantly higher in group 1 (14.7 kPa) than in either group 2 (12.7 kPa) or group 3 (9.3 kPa) (P < 0.01). In the evaluation of the receiver operating characteristic curve, the cutoff value was discovered to be 14.3 kPA (95% CI: 0.753–0.995) in the acute appendicitis group, with a 100% sensitivity and 79.17% specificity. Shear wave elastography examination is not considered an invasive method and is an easily accessible diagnostic tool that can be used to differentiate between inflamed and noninflamed tissue in children. The quantitative measurement for flexibility of the appendix contributes to the diagnosis.
Assessment of spontaneous brain activity patterns in patients with iridocyclitis: a resting-state study
Authors: Tong Yan , Huang Xin , Qi Chen-Xing , Shen Yin
Published: April 2021

Several studies demonstrated that patients with iridocyclitis were associated with vision loss and cognitive decline, whereas alterations in spontaneous brain activity occur in iridocyclitis patients remains unknown. The study aimed to explore spontaneous brain activity changes in iridocyclitis patients. Twenty-six patients with iridocyclitis and 26 healthy controls were finally included in our study. Resting-state MRI (rs-MRI) scan was conducted on both groups and the whole brain amplitude of low-frequency fluctuations (ALFFs) value was collected to assess differences in spontaneous brain activity. A receiver operating characteristic (ROC) curve was analyzed to distinguish between the fMRI data of patients with iridocyclitis and healthy controls. Patients with iridocyclitis showed significantly lower ALFF values in the right inferior parietal lobule, right calcarine, right superior temporal gyrus and right precentral gyrus compared to healthy controls and significantly higher ALFF values in the left superior frontal gyrus (P < 0.01, false discovery rate correction). The ROC curve analysis of different brain areas showed that the accuracies of ALFF value specificity between the iridocyclitis and healthy controls of the area under the curve were over 0.8. Our study highlighted an altered spontaneous activity in multiple brain regions, including the visual cortex, default-mode network, auditory area and sensorimotor areas in iridocyclitis. This may provide valuable information about underlying pathogenic mechanisms of iridocyclitis. These findings also indicate that rs-fMRI serves as a potential tool in the disease detection and evaluation of neurologic impairment in iridocyclitis.
Estimating the strength of selection for new SARS-CoV-2 variants
Authors: van Dorp Christiaan H. , Goldberg Emma E. , Hengartner Nick , Ke Ruian , Romero-Severson Ethan O.
Published: April 2021

Controlling the SARS-CoV-2 pandemic becomes increasingly challenging as the virus adapts to human hosts through the continual emergence of more transmissible variants. Simply observing that a variant is increasing in frequency is relatively straightforward, but more sophisticated methodology is needed to determine whether a new variant is a global threat and the magnitude of its selective advantage. We present three methods for quantifying the strength of selection for new and emerging variants of SARS-CoV-2 relative to the background of contemporaneous variants. These methods range from a detailed model of dynamics within one country to a broad analysis across all countries, and they include alternative explanations such as migration and drift. We find evidence for strong selection favoring the D614G spike mutation and B.1.1.7 (Alpha), weaker selection favoring B.1.351 (Beta), and no advantage of R.1 after it spreads beyond Japan. Cutting back data to earlier time horizons reveals large uncertainty very soon after emergence, but that estimates of selection stabilize after several weeks. Our results also show substantial heterogeneity among countries, demonstrating the need for a truly global perspective on the molecular epidemiology of SARS-CoV-2.