bluuebunny/crossref_metadata_2025 huggingface dataset:
PRODORIC: state-of-the-art database of prokaryotic gene regulation
Authors: Dudek Christian-Alexander , Jahn Dieter
Published: November 2021

PRODORIC is worldwide one of the largest collections of prokaryotic transcription factor binding sites from multiple bacterial sources with corresponding interpretation and visualization tools. With the introduction of PRODORIC2 in 2017, the transition to a modern web interface and maintainable backend was started. With this latest PRODORIC release the database backend is now fully API-based and provides programmatical access to the complete PRODORIC data. The visualization tools Genome Browser and ProdoNet from the original PRODORIC have been reintroduced and were integrated into the PRODORIC website. Missing input and output options from the original Virtual Footprint were added again for position weight matrix pattern-based searches. The whole PRODORIC dataset was reannotated. Every transcription factor binding site was re-evaluated to increase the overall database quality. During this process, additional parameters, like bound effectors, regulation type and different types of experimental evidence have been added for every transcription factor. Additionally, 109 new transcription factors and 6 new organisms have been added. PRODORIC is publicly available at https://www.prodoric.de.
CEBS update: curated toxicology database with enhanced tools for data integration
Authors: Martini Cari , Liu Ying Frances , Gong Hui , Sayers Nicole , Segura German , Fostel Jennifer
Published: November 2021

The Chemical Effects in Biological Systems database (CEBS) contains extensive toxicology study results and metadata from the Division of the National Toxicology Program (NTP) and other studies of environmental health interest. This resource grants public access to search and collate data from over 10 250 studies for 12 750 test articles (chemicals, environmental agents). CEBS has made considerable strides over the last 5 years to integrate growing internal data repositories into data warehouses and data marts to better serve the public with high quality curated datasets. This effort includes harmonizing legacy terms and metadata to current standards, mapping test articles to external identifiers, and aligning terms to OBO (Open Biological and Biomedical Ontology) Foundry ontologies. The data are made available through the CEBS Homepage (https://cebs.niehs.nih.gov/cebs/), guided search applications, flat files on FTP (file transfer protocol), and APIs (application programming interface) for user access and to provide a bridge for computational tools. The user interface is intuitive with a single search bar to query keywords related to study metadata, publications, and data availability. Results are consolidated to single pages for each test article with NTP conclusions, publications, individual studies, data collections, and links to related test articles and projects available together.
Pediatric hallux valgus: An overview of history, examination, conservative, and surgical management
Authors: Seidenstein Alexandra H , Torrez Timothy W , Andrews Nicholas A , Patch David A , Conklin Michael J , Shah Ashish
Published: November 2021

Pediatric hallux valgus (PHV), while relatively rare, is still often encountered by general pediatricians. Herein, we concisely summarize the existing literature regarding the pathogenesis, associated conditions, clinical diagnosis, radiographic characteristics, conservative management, and surgical management of PVH. Though PHV is generally considered benign, the progression of hallux valgus can result in complications. The presence of an open physis in the pediatric age group delineates first line treatment choices, whenever possible, as nonoperative. The general exception to this recommendation is for children with neuromuscular and connective tissues disease who may benefit from earlier surgical management. If conservative approaches fail prior to skeletal maturity, the risk of recurrence and need for revision surgery should be discussed with patients and their families before surgical referral is made. The current review was conducted to aid primary care providers in better understanding the pathogenesis, associated conditions, and intervention options available to manage PHV.
Chloroplast membrane lipid remodeling protects against dehydration by limiting membrane fusion and distortion
Authors: Chng Choon-Peng , Wang Kun , Ma Wei , Hsia K Jimmy , Huang Changjin
Published: November 2021

Dehydration damages the structural integrity of the chloroplast membrane and, consequently, the normal photosynthetic function of this organelle. Remodeling of galactolipids by converting monogalactosyl–diacylglycerol (MGDG) to digalactosyl-diacylglycerol (DGDG) and oligo-galactolipids is an effective adaptation strategy for protecting against dehydration damage to the chloroplast membrane. However, detailed molecular mechanisms are missing. In this study, by performing molecular-level simulations of bi-lamellar membranes under various dehydration conditions, we find that MGDG-to-DGDG remodeling protects the chloroplast membrane in a unique manner by simultaneously dictating both the extent and the pattern of fusion stalks formed with the apposed membrane. Specifically, MGDG-rich membranes form elongated stalks at a moderate dehydration level, whereas DGDG-rich membranes form smaller, rounded stalks. Simulations of wild-type and mutant Arabidopsis (Arabidopsis thaliana) outer chloroplast membranes further confirm that the mutant membrane without galactolipid remodeling is more susceptible to membrane fusion due to its higher MGDG content. Our work reveals the underlying physical mechanisms that govern the pattern and extent of membrane fusion structures, paving the way for rational genetic engineering of crops with improved dehydration tolerance.
Impact of contraceptive coverage policies on contraceptive use and risky sexual behavior among adolescent girls in the USA
Authors: Paul Pooja L , Pace Lydia E , Hawkins Summer Sherburne
Published: November 2021

Objective

This study used representative data to examine the impact of changes in contraceptive coverage policies (contraceptive insurance mandates and pharmacy access to emergency contraception) on contraceptive use and risky sexual behavior among adolescent girls.

Study design

Using 2003–17 Youth Risk Behavior Survey data on 116 180 adolescent girls from 34 states, we conducted difference-in-differences models to examine changes in contraceptive use and unprotected sexual intercourse with the implementation of contraceptive coverage policies. We also tested interactions between age and pharmacy access to emergency contraception.

Results

Findings indicate that contraceptive insurance mandates and pharmacy access to emergency contraception were not associated with changes in contraceptive use or unprotected sexual intercourse among adolescent girls, although some changes were observed in specific age groups. Despite this, our results show an overall increase in reported use of birth control pills and longer-acting methods from 2003 through 2017.

Conclusions

Using representative data, this study lends support to existing evidence that increased access to emergency contraception does not impact contraceptive method used or unprotected sexual intercourse among adolescent girls. The results underscore the need for expanding access to a wide range of contraceptive options for adolescents, with a focus on safer and more effective longer-acting methods.
The Macroeconomics of Sticky Prices with Generalized Hazard Functions
Authors: Alvarez Fernando , Lippi Francesco , Oskolkov Aleksei
Published: November 2021

We give a full analytic characterization of a large class of sticky-price models where the firm’s price-setting behavior is described by a generalized hazard function. Such a function allows for a vast variety of empirical hazards to be fitted. This setup is microfounded by random adjustment costs, as in Caballero and Engel (1999), or by information frictions, as in Woodford (2009). We establish two main results. First, we show how to identify all the primitives of the model, including the distribution of the fundamental adjustment costs and the implied generalized hazard function, using the distribution of price changes. Second, we derive a sufficient statistic for the aggregate effect of a monetary shock: given an arbitrary generalized hazard function, the cumulative impulse response of output to a once-and-for-all monetary shock is proportional to the ratio of the kurtosis of the steady-state distribution of price changes over the frequency of price adjustment. We prove that Calvo’s model yields the upper bound and Golosov and Lucas’s model the lower bound on this measure in the class of random menu cost models.
The Heterogeneous Effect of COVID-19 on the Gender Gap in Iran
Authors: Yousefi Kowsar , Pilvar Hanifa , Farajnia Salman
Published: November 2021

COVID-19 has impacted all human beings, but more severely people with baseline vulnerabilities, and especially women. The impact is even more pronounced in developing countries where gender gap bias is more acute. We use the national data set of the Labor Force Survey, from 2015 to summer 2020, to assess the heterogeneous impacts of the downturn on the employment of women in Iran. Findings show that women have disproportionately exited the labor market, which widens the gender gap in the participation rate. They also show a slower recovery for women compared to men. In contrast, when remaining in the labor market women’s working hours are less affected than men’s. Overall, our findings show a heterogeneous effect from the pandemic among women regarding their education level, age, and occupational choices.
Perinatal Outcomes in Singleton Pregnancies After In Vitro Fertilization Cycles Over 24 Years
Authors: Shah Jaimin S. , Vaughan Denis A. , Leung Angela , Korkidakis Ann , Figueras Francesc , Garcia Desiree , Penzias Alan S. , Sakkas Denny
Published: November 2021

(Abstracted from Fertil Steril 2021;116(1):27–35)

In vitro fertilization (IVF) has represented the mainstay of infertility treatment globally for many decades and has improved significantly over this time in efficacy and efficiency. Innovation in technology and laboratory practices such as cryopreservation and vitrification in conjunction with clinical alterations in protocols and embryo transfer (ET) number have played an important role in the advancement of IVF.
Treatment of Platinum Nonresponsive Metastatic Malignant Peritoneal Mesothelioma With Combination Chemoimmunotherapy
Authors: Foote Michael B. , Shia Jinru , Zauderer Marjorie G. , Nash Garrett M. , Cercek Andrea
Published: November 2021

Malignant peritoneal mesothelioma is a rare cancer associated with minimal durable disease control with chemotherapy and poor overall survival. The efficacy of combined cytotoxic chemotherapy and immune checkpoint inhibitors (ICIs) in malignant peritoneal mesothelioma has not previously been studied. We describe the clinical course of 2 patients with metastatic peritoneal mesothelioma who both relapsed with platinum nonresponsive disease after initial cytoreductive surgery and chemotherapy. In both cases, addition of pembrolizumab to platinum and pemetrexed treatment resulted in a substantial partial and a near complete disease response. Notably, both patients possessed tumors without validated biomarkers of ICI response, including low tumor mutational burden and negative programmed death ligand-1. The unique genomic landscape of each patient may have enabled increased tumor immunorecognition and ICI efficacy. In addition, chemotherapy priming of the tumor microenvironment may have improved ICI response. This report supports future research to characterize the benefit of combination chemotherapy and ICI in peritoneal mesothelioma.
Atypical atrial flutter: review of mechanisms, advances in mapping and ablation outcomes
Authors: Ko Ko Nway Le , Sriramoju Anil , Khetarpal Banveet Kaur , Srivathsan Komandoor
Published: November 2021

Purpose of review

Atrial flutter (AFL) is the second most prevalent arrhythmia after atrial fibrillation (AF). It is a macro-reentrant tachycardia that is either cavotricuspid isthmus dependent (typical) or independent (atypical). This review aims at highlighting mechanism, diagnosis and treatment of atypical AFL and the recent developments in electroanatomic mapping.

Recent findings

Incidence of left AFL is at an exponential rise presently with increase in AF ablation rates. The mechanism of left AFL is most often peri-mitral, roof-dependent or within pulmonary veins in preablated, in contrast to posterior or anterior wall low voltage areas in ablation naïve patients. Linear lesions, compared to pulmonary vein isolation alone, have higher incidence of atypical right or left AFL. Catheter ablation for atypical AFL is associated with lower rates of thromboembolic events, transfusions, and length of stay compared to typical AFL.

Advances in mapping have allowed rapid simultaneous acquisition of automatically annotated points in the atria and identification of details of macro-reentrant circuits, including zones of conduction block, scar, and slow conduction.
Arrhythmogenic right ventricular cardiomyopathy in the pediatric population
Authors: Cohen Mitchell I. , Atkins Melany B.
Published: November 2021

Purpose of review

Review the current state of the art of arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosis and risk stratification in the pediatric population.

Recent findings

ARVC is an inherited cardiomyopathy characterized by progressive myocyte loss and fibrofatty replacement of predominantly the right ventricle and high risk of ventricular arrhythmias and sudden cardiac death (SCD). ARVC is one of the leading causes of arrhythmic cardiac arrest in young people. Early diagnosis and accurate risk assessment are challenging, especially in children who often exhibit little to no phenotype, even if genotype positive. Multimodal imaging provides more detailed assessment of the right ventricle and has been shown in pediatric patients to identify earlier preclinical disease expression. Identification of patients with ARVC allows the clinician to intervene early with appropriate exercise restrictions, even if genotype positive only without phenotypic expression. Emphasis should be placed on stratifying the patient's risk of ventricular arrhythmias and SCD.

ARVC is a challenging diagnosis to make in adolescents who often do not exhibit clinical symptoms. Newer multimodal imaging techniques and improvements in genetic testing and biomarkers should help improve early diagnosis. Exercise restriction for children with ARVC has been shown to reduce disease advancement and decreases the risk of a life-threatening event.
RESTORATION PROCESS OF THE OUTER RETINAL LAYERS AFTER SURGICAL MACULAR HOLE CLOSURE
Authors: Iwasaki Masanori , Ando Ryo , Aoki Shuichiro , Miyamoto Hirotomo
Published: November 2021

Purpose:

To investigate the interrelationship among the outer retinal layers after macular hole surgery and elucidate the restoration process.

Methods:

This retrospective observational study included 50 eyes of 47 consecutive patients with closed macular holes in the first vitrectomy. Optical coherence tomography was obtained before surgery; at 1, 3, and 6 months postsurgery; and at the last visit. The complete continuous layer rate and mean defect length were evaluated for the outer nuclear layer (ONL), external limiting membrane (ELM), and ellipsoid zone (EZ).

Results:

At all postoperative visits, the complete continuous layer rate was in the descending order of ELM, ONL, and EZ and the mean defect length was in the ascending order of ELM, ONL, and EZ. External limiting membrane was necessary for ONL restoration. External limiting membrane and ONL were necessary for EZ restoration. Hyperreflective protrusions were observed from the area lacking ELM into the subretinal space after surgery. Ellipsoid zone was not formed in coexistence with the hyperreflective protrusions. Intermediate reflective protrusions appeared under the ONL plus ELM after surgery and were eventually replaced by EZ.

Conclusion:

Restoration of the outer retinal layers after surgical macular hole closure occurs in the order of ELM, ONL, and EZ.
Evaluation of Silicosis, Asthma, and COPD Among Sand and Gravel and Stone Surface Mine Workers
Authors: TenHarmsel Hailey , Wang Ling , Rosenman Kenneth D.
Published: November 2021

Objective:

Despite the large number of workers in surface sand and gravel mines, there are no previous studies on a cohort of these workers.

Methods:

A cross-sectional study of Michigan surface mine workers included a questionnaire and for those who worked ≥15 years spirometry and chest x-ray.

Results:

Questionnaires were completed by 1207 miners, 111 had an X-ray and 70 had spirometry. There were no silicosis cases. There were 117 with asthma, 22 COPD, 129 saw a doctor for shortness of breath (SOB), 125 with possible work-related asthma, and 26 abnormal spirometry results.

Conclusions:

Although, no cases of silicosis were identified, there was more current asthma; and an association of current asthma, COPD and seeing a doctor for SOB with time since first worked, and obstructive changes in some nonsmokers that suggested the potential for adverse respiratory effects.
COVID Vaccination in Athletes and Updated Interim Guidance on the Preparticipation Physical Examination During the SARS-Cov-2 Pandemic
Authors: Narducci Dusty Marie , Diamond Alex B. , Bernhardt David T. , Roberts William O.
Published: November 2021

The American Medical Society for Sports Medicine (AMSSM) convened an expert panel to address the current evidence, knowledge gaps, and recommendations surrounding the COVID vaccination in athletes during the SARS-CoV-2 pandemic. The group held a series of meetings beginning in July 2021 and reviewed the available literature while using an iterative process and expert consensus to finalize this guidance statement. This document is intended to provide clinicians with suggestions on how to incorporate the COVID vaccination during the preparticipation physical examination for athletes in all levels of training and competition. The statement is not intended to address treatment, infection control principles, safety, ethical discussion, or public health issues related to SARS-CoV-2. The AMSSM task force acknowledges the clinical uncertainty, evolving public health objectives, and the limited data currently available to create this guidance statement.
Marathon Runners' Knowledge and Strategies for Hydration
Authors: Namineni Neeharika , Potok O. Alison , Ix Joachim H. , Ginsberg Charles , Negoianu Dan , Rifkin Dena E. , Garimella Pranav S.
Published: November 2021

Objective:

To study hydration plans and understanding of exercise-associated hyponatremia (EAH) among current marathon runners.

Design:

Cross-sectional study

Setting:

Southern California 2018 summer marathon

Participants:

Two hundred ten marathon runners.

Interventions:

Survey administered 1 to 2 days before the race. Race times were obtained from public race website.

Main Outcome Measures:

Planned frequency of hydration; awareness of, understanding of, and preventative strategies for dehydration and EAH; resources used to create hydration plans; drink preferences.

Results:

When the participants were split into 3 equal groups by racing speed, the slower tertile intended to drink at every mile/station (60%), whereas the faster tertile preferred to drink every other mile or less often (60%), although not statistically significant. Most runners (84%) claimed awareness of EAH, but only 32% could list a symptom of the condition. Both experienced marathoners and the faster tertile significantly had greater understanding of hyponatremia compared with first-time marathoners and the slower tertile, respectively. Less than 5% of marathoners offered “drink to thirst” as a prevention strategy for dehydration or EAH.

Conclusion:

Slower runners plan to drink larger volumes compared with their faster counterparts. Both slower and first-time marathoners significantly lacked understanding of EAH. These groups have plans and knowledge that may put them at higher risk for developing EAH. Most marathon runners did not know of the guidelines to “drink to thirst,” suggesting the 2015 EAH Consensus statement may not have had the desired impact.
“Hepatotoxicity in inflammatory bowel disease: mesalazine, the forgotten drug”
Authors: Garrido Isabel , Santos Ana Luísa , Lopes Joanne , Lopes Susana , Macedo Guilherme
Published: November 2021

Introduction

Mesalazine is a widely prescribed drug, used for the treatment of ulcerative colitis to both induce and maintain remissions in disease. Mesalazine therapy has been associated with a low rate of serum enzyme elevations and a with rare instances of clinically apparent acute liver injury.

Case presentation

A 51-year-old Caucasian woman with ulcerative colitis was treated with mesalazine. Two weeks later, the patient presented severe liver cholestatic injury. No symptoms of generalized hypersensitivity were seen. She had no history of liver disease and was known to have normal routine liver tests before starting treatment. The liver biopsy revealed mild periportal necroinflammatory lesions with no fibrosis, suggestive of drug-induced liver injury. The patient’s symptoms were resolved by discontinuing the mesalazine treatment; within 6 months, all her liver panels returned to normal. After extensively excluding other potential causes of liver injury and with clinical and lab resolution after discontinuing the drug, we assumed mesalazine as the cause of hepatic toxicity.

Conclusion

We describe a patient with ulcerative colitis who developed severe but fully reversible liver cholestatic injury following the prescription of mesalazine. This case reinforces the possibility of a causal relationship between mesalazine therapy and toxic hepatic injury without systemic hypersensitivity. Although it is a usually well-tolerated drug, clinicians should be alert and discontinue therapy when liver dysfunction occurs to avoid the development of chronic hepatitis and liver fibrosis.
Changes in the profile and therapeutic care of people who use drugs with HCV mono-infection: a retrospective study between 2015 and 2019 from a monocentric tertiary referent center in France
Authors: Doffoel Michel , Tripon Simona , Ernwein Florence , Chaffraix Frédéric , Haumesser Lucile , Bader Robert , Lang Jean-Philippe , Lang Anais , Paya Dominique , Royant Maude , Velay-Rusch Aurélie , Tebacher Martine , Meyer Nicolas , Habersetzer François , Baumert Thomas
Published: November 2021

Background and aims

People who use drugs (PWUDs) are the main group at risk for hepatitis C virus (HCV) transmission and a key population for hepatitis C elimination. Multidisciplinary team (MDT) meetings were set up in France in December 2014 within regional reference centers to supervise the prescriptions and delivery of direct-acting antivirals (DAAs) to optimize the management of HCV infection. The aim of this retrospective study was to analyze the changes in the profile and therapeutic care of PWUDs with HCV mono-infection according to the evolution of MDT meetings in a regional tertiary reference center.

Methods

Between 2015 and 2019, overall 1912 HCV-infected patients presented at the MDT meetings, 547 were PWUDs with HCV mono-infection treated with DAAs. Five periods were defined according to the evolution of MDT meetings. The profile and management of PWUDs were compared among these five periods.

Results

Over time, the frequency of advanced stage of fibrosis decreased from 90.8 to 36.3% (P < 0.001), whereas the therapeutic care of the patients in primary addictology centers and networks of general practitioners increased from 17.4 to 55% (P < 0.001). The frequency of excessive alcohol consumption varied between 9.1 and 30% (P = 0.003) and that of opioid substitution therapy between 42.5 and 70% (P < 0.001). The Sustained virologic response assessed 12 weeks after the end of treatment rate was above 95% for the five periods.

Conclusion

Between 2015 and 2019, the changes in the profile and management of PWUDs have followed the evolution of MDT meetings concerning patients with less advanced fibrosis and more therapeutic hepatitis C care made by the primary care centers.
Proceedings of ESPGHAN Monothematic Conference 2020
Authors: Zellos Aglaia , Debray Dominique , Indolfi Giuseppe , Czubkowski Piotr , Samyn Marianne , Hadzic Nedim , Gupte Girish , Fischler Björn , Smets Françoise , de Cléty Stéphan Clément , Grenda Ryszard , Mozer Yael , Mancell Sara , Jahnel Jörg , Auzinger Georg , Worth Austen , Lisman Ton , Staufner Christian , Baumann Ulrich , Dhawan Anil , Alonso Estelle , Squires Robert H. , Verkade Henkjan J.
Published: November 2021

Objectives:

The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to educate pediatric gastroenterologists, members of ESPGHAN and professionals from other specialties promoting an exchange of clinical expertise in the field of pediatric hepatology. Herewith we have concentrated on detailing the recent advances in acute liver failure in infants and children.

Methods:

The 2020 ESPGHAN monothematic three‐day conference on pediatric hepatology disease, entitled “acute liver failure” (ALF), was organized in Athens, Greece. ALF is a devastating disease with high mortality and most cases remain undiagnosed. As knowledge in diagnosis and treatment of ALF in infants and children has increased in the past decades, the objective was to update physicians in the field with the latest research and developments in early recognition, curative therapies and intensive care management, imaging techniques and treatment paradigms in these age groups.

Results:

In the first session, the definition, epidemiology, various causes of ALF, in neonates and older children and recurrent ALF (RALF) were discussed. The second session was dedicated to new aspects of ALF management including hepatic encephalopathy (HE), coagulopathy, intensive care interventions, acute on chronic liver failure, and the role of imaging in treatment and prognosis. Oral presentations by experts in various fields are summarized highlighting key learning points.

Conclusions:

The current report summarizes the major learning points from this meeting. It also identifies areas where there is gap of knowledge, thereby identifying the research agenda for the near future.
Proceedings of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition Monothematic Conference, 2020
Authors: Zellos Aglaia , Debray Dominique , Indolfi Giuseppe , Czubkowski Piotr , Samyn Marianne , Hadzic Nedim , Gupte Girish , Fischler Björn , Smets Françoise , Clément de Cléty Stéphan , Grenda Ryszard , Mozer Yael , Mancell Sara , Jahnel Jörg , Auzinger Georg , Worth Austen , Lisman Ton , Staufner Christian , Baumann Ulrich , Dhawan Anil , Alonso Estelle , Squires Robert H. , Verkade Henkjan J.
Published: November 2021

Objectives:

The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to educate pediatric gastroenterologists, members of ESPGHAN and professionals from other specialties promoting an exchange of clinical expertise in the field of pediatric hepatology.

Methods:

The 2020 single topic ESPGHAN monothematic 3‐day conference on pediatric liver disease, was organized in Athens, Greece and was entitled “ Acute Liver Failure” (ALF). ALF is a devastating disease with high mortality and in a considerable fraction of patients, the cause remains unresolved. As knowledge in diagnosis and treatment of ALF in infants and children has increased in the past decades, the objective was to update physicians in the field with developments in medical therapy and indications for liver transplantation (LT) and to identify areas for future research in clinical and neurocognitive outcomes in ALF.

Results:

We recently reported the epidemiology, diagnosis, and initial intensive care management issues in separate manuscript. Herewith we report on the medical treatment, clinical lessons arising from pediatric studies, nutritional and renal replacement therapy (RRT), indications and contraindications for LT, neurocognitive outcomes, new techniques used as bridging to LT, and areas for future research. Oral presentations by experts in various fields are summarized highlighting key learning points.

Conclusions:

The current report summarizes the current insights in medical treatment of pediatric ALF and the directions for future research.
Measuring Histologic Activity in Inflammatory Bowel Disease: Why and How
Authors: Pai Reetesh K. , Lauwers Gregory Y. , Pai Rish K.
Published: November 2021

Histology is used to confirm the diagnosis of inflammatory bowel disease, exclude superimposed infections, and to evaluate for dysplasia. Histology has rarely been used to measure disease activity and guide therapy despite evidence that histologic measurements have value in predicting important clinical outcomes. More recently, there have been numerous studies supporting a role for histologic disease activity measurements in predicting a variety of outcomes including relapse, hospitalizations, steroid use, and dysplasia. The histologic assessment was superior to endoscopic measurements in many of these studies. This review will summarize the recent literature regarding histologic disease activity measurements in ulcerative colitis and Crohn disease. A detailed description of histologic scoring systems will also be provided to provide pathologists with the necessary tools to accurately measure disease activity.
NTRK-Fusion Sarcoma of the Uterine Cervix: Report of 2 Cases With Comparative Clinicopathologic Features
Authors: Nilforoushan Neshat , Wethington Stephanie L. , Nonogaki Hiro , Gross John , Vang Russell , Xing Deyin
Published: November 2021

NTRK1/2/3 rearrangements have been identified as oncogenic drivers in a variety of tumors including those in the uterine cervix, and rarely, the uterine corpus. We report 2 cases of cervical sarcoma with NTRK gene rearrangements. Case 1 was a 54-yr-old woman who presented with postmenopausal bleeding and a 5.4 cm friable mass in the cervix. Microscopic examination of the tumor revealed proliferation of epithelioid and spindle cells arranged in alternating hypercellular and hypocellular areas, with subtle fibrosarcoma-like features. Coagulative tumor cell necrosis and readily recognizable mitoses (up to 40 mitotic figures per 10 high-power fields) were identified. Case 2 was a 52-yr-old woman who presented with abnormal vaginal bleeding and a 1.3 cm cervical mass. The resected cervical tumor showed proliferation of spindled cells with fascicular and storiform growth pattern, infiltrating into the smooth muscle with entrapment of normal endocervical glands. The tumor cells displayed mild cytologic atypia and low mitotic activity (1 mitotic figure per 10 high-power fields). The mixed inflammatory infiltrate was seen throughout the lesion, mimicking morphology of inflammatory myofibroblastic tumor. Immunohistochemical staining for S100 and CD34 demonstrated variable expression in case 1 and uniformly diffuse positivity in case 2. The tumor cells in both cases were focally positive for CD10, Cyclin D1, ER, and PR, and negative for AE1/AE3, desmin, SOX10, HMB-45. RNA fusion analysis identified SPECC1L-NTRK3 gene rearrangements in case 1 and TPM3-NTRK1 in case 2; DNA-based mutational analysis also revealed CDKN2A/B homozygous deletion in case 1. Despite accumulating literature on NTRK fusion mesenchymal tumors in gynecologic pathology, these tumors are still rare and lack well-established morphologic diagnostic criteria. Diagnostic and clinical recognition of these tumors is critical given the potential patient benefit from targeted therapy.
The Relationship Between Objectively Measured Step Count, Clinical Characteristics, and Quality of Life Among Depressed Patients Recently Hospitalized With Systolic Heart Failure
Authors: Holber Julia P. , Abebe Kaleab Z. , Huang Yan , Jakicic John M. , Anderson Amy M. , Belnap Bea Herbeck , Rollman Bruce L.
Published: November 2021

Objective

Physical activity (PA) can improve symptoms of both depression and heart failure (HF), but objective activity data among recently hospitalized HF patients with comorbid depression are lacking. We examined PA and the relationship between daily step counts and mood, health-related quality of life (HRQoL), and heart health among patients enrolled in a clinical trial treating HF and comorbid depression.

Methods

We screened hospitalized patients with systolic HF (left ventricular ejection fraction [LVEF] ≤45%) and New York Heart Association class II–IV symptoms for depression using the two-item Patient Health Questionnaire (PHQ-2) and telephoned screen-positive patients to administer the PHQ-9 2 weeks after discharge. If the patient scored PHQ-9 ≥10 and agreed to continue in our study, we administered our baseline assessment and mailed them an armband accelerometer. We instructed patients to wear the armbands for 7 days before returning them and classified their data as “usable” if they wore it ≥10 hours per day on ≥4 separate days.

Results

We mailed accelerometers to 531 depressed HF patients, and 222 (42%) returned them with usable data. Their median age was 64 years, 54% were women, 23% were non-White, and they walked a median of 1170 steps daily. Higher median daily step counts were associated with lower New York Heart Association class and better physical- and HF-specific HRQoL, but not mood symptoms, mental HRQoL, or LVEF.

Conclusions

Patients with HF and comorbid depression are generally sedentary after hospital discharge. Although mood symptoms and LVEF were unrelated to objective PA, patients with higher step counts self-reported better HRQoL.

Trial Registration:
ClinicalTrials.gov identifier NCT02044211.
Hyperhidrosis of the residual limb: a narrative review of the measurement and treatment of excess perspiration affecting individuals with amputation
Authors: Lannan Ford M. , Powell Jordan , Kim Gabriel M. , Hansen Colby R , Pasquina Paul F. , Smith Douglas G.
Published: November 2021

Background:

Hyperhidrosis (HH) is a relatively common disorder involving excessive sweating, typically of the palms or axilla. HH can also frequently occur after limb amputation, where the remaining residual limb excessively perspires, leading to an increased risk of dermatological disorders and functional limitations, such as the inability to comfortably or safely wear a prosthesis. Although many treatments have been proposed to treat HH within the dermatology community, they are not widely known by healthcare providers typically involved in caring for individuals with acquired limb loss.

Objectives:

To appraise the current state of quantitative and qualitative assessment of HH within the residual limb and examine existing and future treatment strategies for this problem.

Study design:

Narrative Literature Review.

Methods:

A literature review focused on the assessment and treatment of excessive sweating of residual limbs.

Results:

There is currently no objective or subjective standard to assess or diagnose HH of the residual limb. Conventional therapies for HH do not always translate to the population of individuals with limb loss. Emerging modalities for treating HH show promise toward a permanent resolution of excess perspiration but require additional studies within people with amputation.

Conclusions:

Further research is needed to quantify standard values to objectively and subjectively assess and diagnose hyperhidrosis of the residual limb. New and developing treatments for hyperhidrosis require additional studies to assess efficacy and safety in the residual limb.
Prefabricated ankle-foot orthoses for children with cerebral palsy to overcome spastic drop-foot: does orthotic ankle stiffness matter?
Authors: Böhm Harald , Dussa Chakravarthy U.
Published: November 2021

Background:

Spastic drop-foot is a common problem in children with cerebral palsy that may lead to tripping and falling. To improve ankle dorsiflexion in swing phase, prefabricated carbon-composite ankle-foot orthoses are commonly prescribed; by increasing ankle stiffness, these orthoses may also improve knee extension in stance.

Objectives:

To compare the effect of a stiff vs. flexible prefabricated ankle-foot orthosis on sagittal plane ankle and knee kinematics and kinetics during walking.

Study design:

Cross-sectional, repeated-measures, interventional study.

Methods:

Twenty-seven children and adolescents with cerebral palsy who had drop-foot in swing were included. Gait analysis was conducted under four conditions: barefoot, shod, with a stiff, and with a flexible orthosis. Participants were divided into two groups including children and adolescents who have a flexed knee during stance (KF, N = 12) and without flexed knee during stance (KE, N = 15).

Results:

Ankle dorsiflexion in swing phase was significantly improved compared with the shod condition by 6.3 degrees (SD = 3.3 degrees) only in the KE group when using the flexible orthosis. For the stiff orthosis, knee extension in stance was significantly increased by 2.4 degrees (SD = 3.3 degrees) in the KE group compared with the shod condition. No significant improvements were observed for the KF group. Further analysis indicated that only seven patients in the KF group with weak ankle plantarflexors improved knee extension while using the stiff orthosis.

Conclusions:

Our results suggested that in the KE group, the flexible orthosis was best suited for patients with drop-foot without a knee extension deficit. The stiff orthosis was not suitable in this group as it caused a hyperextended knee without improving dorsiflexion in swing phase. Therefore, stiffness should be considered when prefabricated orthoses are prescribed.
Comparison of Ultrasound Features With Maximum Standardized Uptake Value Assessed by 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography for Prognosis of Estrogen Receptor+/Human Epithelial Growth Factor Receptor 2− Breast Cancer
Authors: Choi Bobae
Published: November 2021

estrogen receptor (ER)+/human epithelial growth factor receptor 2 (HER2)− breast cancers have less aggressive traits and a favorable prognosis when treated early. Prediction of prognosis for treatment outcome or survival in ER+/HER2− cancer is important. Ultrasound (US) is an effective and easy technique for breast cancer diagnosis and tumor characterization. Positron emission tomography/computed tomography (PET/CT) is widely used for diagnosis, staging, and therapeutic response in cancer evaluation, and a high maximum standardized uptake value (SUVmax) is associated with poor prognosis. The study aim was to compare the prognostic value of US features with that of the SUVmax assessed by PET/CT in ER+/HER− breast cancer patients. We retrospectively identified breast cancer patients in our institutional database who had undergone preoperative US and PET/CT, and 96 patients with invasive ductal carcinoma and ductal carcinoma in situ were included in this study. The US features of mass shape, margin, echo pattern, orientation, posterior features, boundary, and calcification in the mass were analyzed. We then analyzed the US features to look for correlations with SUVmax and associations with margins, boundaries, posterior features, histological grade, and ki-67 expression. High SUVmax was correlated with irregular shape, not-circumscribed margin, posterior acoustic enhancement, echogenic halo, and calcification in the mass (P < 0.05, all). Posterior acoustic enhancement was correlated with high ki-67 expression. Many US features of ER+/HER− breast cancer showed associations with SUVmax. Some US features of ER+/HER− breast cancer were useful for predicting prognosis.
The MHC-characterized Miniature Swine: Lessons Learned From a 40-Year Experience in Transplantation
Authors: Matar Abraham J. , Sachs David H. , Duran-Struuck Raimon
Published: November 2021

Over the last 40 y, a specialized herd of miniature swine has been intentionally bred to develop lines of animals homozygous for the swine major histocompatibility complex (MHC), which have facilitated transplantation studies across reproducible MHC and minor antigen mismatch barriers. These MHC-characterized miniature swine (Mc-MS) have been used for the study of novel surgical techniques, various approaches to tolerance induction of solid organ and vascularized composite allografts, as well as studies of the immunobiology of allografts and xenografts. Mc-MS possess characteristics that are highly advantageous to these studies, and their continued use will likely continue to play an important role in bridging “bench-to-cage-to bedside” therapies in the field of transplantation. In this review, we highlight the seminal contributions of the Mc-MS model to the field and analyze their role in the broader context of large animal models in transplantation research.
A dual larynx motor networks hypothesis
Authors: Belyk Michel , Eichert Nicole , McGettigan Carolyn
Published: November 2021

Humans are vocal modulators par excellence. This ability is supported in part by the dual representation of the laryngeal muscles in the motor cortex. Movement, however, is not the product of motor cortex alone but of a broader motor network. This network consists of brain regions that contain somatotopic maps that parallel the organization in motor cortex. We therefore present a novel hypothesis that the dual laryngeal representation is repeated throughout the broader motor network. In support of the hypothesis, we review existing literature that demonstrates the existence of network-wide somatotopy and present initial evidence for the hypothesis' plausibility. Understanding how this uniquely human phenotype in motor cortex interacts with broader brain networks is an important step toward understanding how humans evolved the ability to speak. We further suggest that this system may provide a means to study how individual components of the nervous system evolved within the context of neuronal networks.

This article is part of the theme issue ‘Voice modulation: from origin and mechanism to social impact (Part I)’.
Rethinking the frequency code: a meta-analytic review of the role of acoustic body size in communicative phenomena
Authors: Winter Bodo , Oh Grace Eunhae , Hübscher Iris , Idemaru Kaori , Brown Lucien , Prieto Pilar , Grawunder Sven
Published: November 2021

The widely cited frequency code hypothesis attempts to explain a diverse range of communicative phenomena through the acoustic projection of body size. The set of phenomena includes size sound symbolism (using /i/ to signal smallness in words such asteeny), intonational phonology (using rising contours to signal questions) and the indexing of social relations via vocal modulation, such as lowering one's voice pitch to signal dominance. Among other things, the frequency code is commonly interpreted to suggest that polite speech should be universally signalled via high pitch owing to the association of high pitch with small size and submissiveness. We present a cross-cultural meta-analysis of polite speech of 101 speakers from seven different languages. While we find evidence for cross-cultural variation, voice pitch is on average lower when speakers speak politely, contrary to what the frequency code predicts. We interpret our findings in the light of the fact that pitch has a multiplicity of possible communicative meanings. Cultural and contextual variation determines which specific meanings become manifest in a specific interactional context. We use the evidence from our meta-analysis to propose an updated view of the frequency code hypothesis that is based on the existence of many-to-many mappings between speech acoustics and communicative interpretations.

This article is part of the theme issue ‘Voice modulation: from origin and mechanism to social impact (Part I)’.
Evidence accumulation rate moderates the relationship between enriched environment exposure and age-related response speed declines
Authors: Brosnan Méadhbh B. , O’Neill Megan H. , Loughnane Gerard M. , Pearce Daniel J. , Fleming Bryce , Zhou Shou-Han , Chong Trevor T.-J. , Nobre Anna C. , Connell Redmond G. O , Bellgrove Mark A.
Published: November 2021

Older adults exposed to enriched environments (EE) maintain relatively higher levels of cognitive function, even in the face of compromised markers of brain health. Response speed (RS) is often used as a simple proxy to measure the preservation of global cognitive function in older adults. However, it is unknown which specific selection, decision, and/or motor processes provide the most specific indices of neurocognitive health. Here, using a simple decision task with electroencephalography (EEG), we found that the efficiency with which an individual accumulates sensory evidence was a critical determinant of the extent to which RS was preserved in older adults. Moreover, the mitigating influence of EE on age-related RS declines was most pronounced when evidence accumulation rates were shallowest. These results suggest that the phenomenon of cognitive reserve, whereby high EE individuals can better tolerate suboptimal brain health to facilitate the preservation of cognitive function, is not just applicable to neuroanatomical indicators of brain ageing, but can be observed in markers of neurophysiology. Our results suggest that EEG metrics of evidence accumulation may index neurocognitive vulnerability of the ageing brain.

SIGNIFICANCE STATEMENT

Response speed in older adults is closely linked with trajectories of cognitive ageing. Here, by recording brain activity while individuals perform a simple computer task, we identify a neural metric which is a critical determinant of response speed. Older adults exposed to greater cognitive and social stimulation throughout a lifetime could maintain faster responding, even when this neural metric was impaired. This work suggests EEG is a useful technique for interrogating how a lifetime of stimulation benefits brain health in ageing.
Compartmentalized dendritic plasticity in the retrosplenial cortex integrates memories across time
Authors: Sehgal Megha , Filho Daniel Almeida , Kastellakis George , Kim Sungsoo , Lee Jinsu , Shen Yang , Huang Shan , Lavi Ayal , Fernandes Giselle , Martin Sunaina Soans , Mejia Irene Davila , Pekcan Asli , Wu Melody Shana , Heo Won Do , Poirazi Panayiota , Trachtenberg Joshua T. , Silva Alcino J.
Published: November 2021

Events occurring close in time are often linked in memory, providing an episodic timeline and a framework for those memories. Recent studies suggest that memories acquired close in time are encoded by overlapping neuronal ensembles, but the role of dendritic plasticity mechanisms in linking memories is unknown. Using activity-dependent labeling and manipulation approaches, longitudinal one- and two-photon imaging of somatic and dendritic compartments, and computational modeling, we show that memory linking is not only dependent on ensemble overlap in the retrosplenial cortex, but also on branch-specific dendritic allocation mechanisms. The same dendritic segments are preferentially activated by two linked memories, and spine clusters added after each of the two linked memories are allocated to the same dendritic segments. Our results demonstrate a causal mechanistic role for dendritic plasticity in memory integration and reveal a novel set of rules that govern how linked and independent memories are allocated to dendritic compartments.